What Should You Know About the Role of Surgery in Breast Cancer Treatment?

What Should You Know About the Role of Surgery in Breast Cancer Treatment? from Patient Empowerment Network on Vimeo.

Dr. Stephanie Valente explains how surgery approaches, including mastectomy and lumpectomy, are used in treating breast cancer, and addresses common misconceptions about mastectomy.

Dr. Stephanie Valente is the Director of the Breast Surgery Fellowship Program at Cleveland Clinic. More about this expert here.

See More From The Pro-Active Breast Cancer Patient Toolkit

Related Resources:

 
 

Transcript:

Dr. Valente:            

So, breast cancer patients have the option to remove their whole breast, which is called a mastectomy. And if they pick that option, they could choose to have reconstruction or to essentially go flat. Yes, we have even done reconstruction in metastatic breast cancer patients. Metastatic breast cancer patients live for a really long time, so giving them reconstruction to make them feel whole and kind of put them back together after a mastectomy is definitely a good option.        

The other option is to just remove the cancer. So, if the patient has a small breast cancer, and it’s metastatic, we can just say – Hey, you don’t have to have the whole breast removed. So, we can do a lumpectomy, as well.

So, a lumpectomy is essentially a surgery that removes the cancer with a normal rim of tissue around it. We also call it a partial mastectomy, meaning you’re removing just part of the breast. Or it’s also called breast-conserving surgery. So, it’s any method that removes that cancer with a normal rim of healthy tissue around it but allows the woman to keep her breasts.

So, when it comes to surgical choices and a cancer coming back, some women think that if they pick the most advanced surgery, such as a mastectomy, it helps prevent cancer from going somewhere else in the body. And that’s actually not true. Removing both breasts, doesn’t make you live one day longer. At that point, a mastectomy or a lumpectomy is a choice.

And prognosis – meaning whether or not the cancer’s gonna show up somewhere in the body – is based really on two things – the stage at which the breast cancer presents itself and what type of breast cancer it is – meaning is the cancer outside of the lymph nodes? How large is it? And if it’s a triple negative or some other type of breast cancer? Those determine the higher likelihood that somebody could develop metastatic breast cancer later in their life, even though small, early-stage breast cancers, unfortunately, can also develop metastasis later on in life.

But women sometimes think that if they pick the most aggressive surgery, it’s helping prevent metastatic spread later on in life. And that’s actually not the choice.  Breast cancer surgery is the option that women choose to surgically remove their breast cancer. But again, choosing a mastectomy or a lumpectomy for an early-stage breast cancer is a choice of how they wanna remove the breast cancer. But it doesn’t improve the chances that they won’t have metastatic spread later on.

So, the role of surgery for metastatic breast cancer is mainly for what we call to remove the cancer or sometimes for local control. So, the number one treatment if somebody is diagnosed with metastatic breast cancer is systemic therapy. That might be chemotherapy or endocrine therapy. But it’s really to get the metastatic disease under control.

So, where does breast cancer usually go? Bones, liver, lungs, brain. So, surgery to remove the breast or the breast cancer in the breast doesn’t really take care of those problems. But a lot of times for metastatic cancer, the one reason would be for local control. So, if the cancer is causing issues in the breast – swelling, coming out of the skin – where it’s a wound issue, then we’ll remove that to get better control of the area in the breast.

The other reason is if somebody has metastatic cancer, and their cancer in the other area of their body is controlled with the therapy, then we say – Hey, chemo’s working, or the systemic therapy’s working. The only thing that seems to be left is the area in your breast. Then for a conversation with medical oncology, we say you don’t have to come off your medications. This is a good time to remove the breast cancer to control that problem.

Metastatic Breast Cancer Treatment and Research News

Metastatic Breast Cancer Treatment and Research News from Patient Empowerment Network on Vimeo.

As metastatic breast cancer testing approaches continue to expand, new and promising treatments have emerged. Dr. Lisa Flaum shares information on recently approved treatment options and the role of genetic markers in accessing targeted therapy. 

Dr. Lisa Flaum is a Medical Oncologist at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more here.

See More From The Pro-Active Breast Cancer Patient Toolkit

Related Resources:

 

Transcript:

Dr. Flaum:                  

There are a lot of new and promising treatments for metastatic breast cancer. So, the treatments in general and the novel treatments and studies really vary based on the subset of metastatic breast cancer. So, when we’re making our treatment decisions, a lot of it is defined by those markers. So, if someone has a tumor that is hormone receptor, estrogen and progesterone receptor positive, and HER2-negative, the mainstay of treatment is typically drugs that target estrogen and often partnering drugs that target estrogen with other more novel or newer treatments.

So, just in the last five plus years, there have been a number of new drugs and even new drug categories that we didn’t have previously. So, for that population of the estrogen receptor positive tumors, the biggest breakthrough over the last number of years has been a class of drugs called CDK4/6 inhibitors. So, that includes drugs like Ibrance, Kisqali, Verzenio. And they’ve emerged as a very important and effective and often a recommendation for our first-line treatment for these patients combined with anti-estrogen therapies that have vastly improved outcomes for patients. So, a much higher percentage of patients respond to these drugs, the duration of the responses has extended quite a bit. And importantly, patients tend to tolerate this drug class really, really well.

 So, for many patients starting out with that diagnosis, this type of drug class is going to be part of the discussion. Even in the last year, another drug category has emerged with approval of a new drug called alpelisib, which is something called at PI3 kinase inhibitor. So, again, back to defining the options based on the molecular profile of the tumor. So, this newer oral drug also partnered with anti-estrogen therapy, has been an important breakthrough for the treatment of patients who harbor this specific molecular abnormality. So, important to define whether that’s an option by some of these molecular testing.

There’s also newer drugs and studies of newer drugs that affect the estrogen receptor in different ways than some of our traditional medications.

And this is an ongoing area of significant research. So, that’s the estrogen receptor positive tumors.

For patients who have HER2-positive tumors, these are tumors that tend to be more aggressive, that tend to require more aggressive upfront treatment, which usually involves drugs that specifically target HER2. So, again, defining what’s driving the tumor and hopefully having drugs available that can target that specific abnormality. So, HER2 targeted drugs have evolved quite a bit over the last couple of decades.

Initially, we just had a drug called Herceptin and then a drug called Perjeta or pertuzumab was developed. Then more recently a drug called Kadcyla. And then even in just the last six to 10 months, two new drugs that target that HER2 protein. One of them is called tucatinib, the other one is called Enhertu. They’re not necessarily appropriate for the first line of treatment, but really sort of expands our toolbox in terms of how we treat these types of tumors. And these are developments that have occurred, for one of the drugs, just in the last six months, and the other within the last year. So, a lot of progress.

And then for the third subset of tumors, which are the triple-negative tumors, those are the ones that do not over-express estrogen, do not have estrogen or progesterone receptors, and don’t overexpressed HER2. This has been historically an area of unmet need. So, tumors where we can’t use anti-estrogen therapies, we can’t use HER2 targeted drugs. And so, the main stay has always been chemotherapy. And even for this subset, we’ve had progress.

So, one of the drug classes that’s been approved in the last couple years for triple-negative breast cancers is immunotherapy. So, immunotherapy has gotten a lot of press. It’s been really breakthrough treatment for a lot of different cancers, has lagged behind to some degree in breast cancer, but has become now one of the early treatment options for people with metastatic disease, specifically those that harbor a molecular marker, an immune marker, something called PD-L1. So, another example of the tumor’s biology dictating potentially one of the treatment options.

There have been other drugs that have been approved for triple-negative breast cancers in women who have BRCA mutation, so who have germline genetic predisposition to breast cancer. And that opens another array of treatment tools that have been approved in the last few years. And then more recently, just over the last six months, another drug that’s been approved for triple-negative breast cancer, which is a drug called sacituzumab, again, not first treatment, but something that defines potentially future lines of treatment. So, big picture, there has been a lot of progress that increasingly alters our treatment tools for patients and allows us to have sequential treatments that can be effective if their given treatment is no longer effective.

Metastatic Breast Cancer Treatment Decisions: Which Path is Best for You?

Metastatic Breast Cancer Treatment Decisions: Which Path is Best for You? from Patient Empowerment Network on Vimeo.

 For each metastatic breast cancer patient, there are several variables to consider to access the best treatment path. Dr. Lisa Flaum explains key factors to consider, and discusses how the risks and benefits are weighed when making treatment decisions for an individual patient.

Dr. Lisa Flaum is a Medical Oncologist at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more here.

See More From The Pro-Active Breast Cancer Patient Toolkit

Related Resources:

 

Transcript:

Dr. Flaum:                  

So, when we’re determining a treatment approach, there are a number of variables. So, to some degree, based on a patient’s individual characteristics, their age, their other health issues, may guide what treatments are available or indicated or even desirable from a patient’s standpoint. To some degree, the locations and extent of disease are important. So, if someone has cancer and that’s causing a particular symptom, with bony sites being a particular example, there may be a role for something targeted; Something like radiation, and in rare cases, surgery to target a specific symptomatic or worrisome spot of metastatic cancer.

In general, the mainstay of treatment for metastatic breast cancer is what we call systemic treatment or medical treatment, treatment that’s going to go everywhere and treat the cancer wherever it is. In some situations, we may be deciding between more or less aggressive treatment, and the locations and sites of disease may be important in determining that. If someone has extensive disease, for instance in a vital organ like the lung, the liver, the brain, we may start with something more versus less aggressive to try to get it better under control quickly. Whereas people with more limited metastatic disease may be able to start with something less aggressive.

And then beyond that, a lot of the decision-making is based on those molecular markers that I alluded to, which are defined by the hormone receptor status. So, whether the tumor expresses those estrogen and progesterone receptors, and whether the tumor over-expresses HER2. And then to a lesser degree, based on other markers that may be defined by additional tests.

So, every treatment discussion we have is a two-way street. So, our job is to present the data, present options, present recommendations. And often, we have an opinion on where we would fall and if there are a number of different options. But to me, it’s a collaborative discussion. And if there are options, it’s weighing what potential benefit do we get from a single option or from adding something to that particular option versus what are the downsides? And some of it is discussion about logistics. Do we do something IV versus oral? Is there a particular side effect that we’re hoping to avoid, such as hair loss? Which of course, we’re trying to avoid. Some treatments may have a higher likelihood of working, but a higher likelihood of causing hair loss. That may factor into our decision.

So, whether it’s the first decision point when we’re deciding on preliminary therapy or future decision points as we go through this journey, there is always a discussion about this is where we are, these are what our options are. Here’s how we’re going to weigh the pros and cons. And then it comes back to a collaborative decision about how we weigh the risks and rewards and where we’re going with an individual patient.

So, clinical trials are always part of at least the conversation, so they’re always a consideration at each step of our discussion. So, from a preliminary treatment standpoint, we’re always going to go through here are our standard options. Here’s, again, what we think is most appropriate. And if there’s a clinical trial that’s appropriate in that scenario, we’ll lay that out there as an option. So, a clinical trial is always worth discussing. It’s always worth asking that your doctor, “Is a clinical trial appropriate for me at this point?” But it’s not always the right recommendation.

So, there are a lot of scenarios, especially at the beginning of treatment for metastatic disease where we have so many options, and so many new and novel treatment options and drugs that have been approved fairly recently that have defined the standard of care, that the standard is going to be often what we recommend. And a clinical trial may be something that we would use if that treatment fails to work or at some future point down the line. And at other points in time, we have very good, appropriate clinical trials that could be indicated at any step along the way. So, it’s worth the discussion. Whether it’s the recommendation or not depends on the circumstances, it depends on the time. What we have today was very different than what we might’ve had available six months ago and six months from now. But clinical trials are out there, and if the location that a patient is going doesn’t have access to clinical trials, it’s always reasonable to ask too, “Should I be going somewhere else to see if a clinical trial is appropriate?”

What Could Advances in Breast Cancer Research Mean for You?

What Could Advances in Metastatic Breast Cancer Research Mean for You? from Patient Empowerment Network on Vimeo.

What should metastatic breast cancer patients know about emerging approaches to treatment and care? Dr. Julie Gralow reviews developments in metastatic breast cancer research, including advances in genetics, subsetting disease and personalized medicine.

Dr. Julie Gralow is the Jill Bennett Endowed Professor of Breast Medical Oncology at the University of Washington, Fred Hutchinson Cancer Research Center, and the Seattle Cancer Care Alliance. More about this expert here.

See More From INSIST! Metastatic Breast Cancer

Related Resources:

 

What Could Metastatic Breast Cancer Genetic Testing Advances Mean for You?

What Are Essential Genetic Tests for Metastatic Breast Cancer Patients?

Metastatic Breast Cancer: Debunking Common Misconceptions

 

Transcript:

Katherine:                  

There have been so many advances in breast cancer research. What are you excited about in research right now?

Dr. Gralow:                

Well, every single drug that’s been approved, every single new regimen that’s been approved in breast cancer is the direct result of clinical trials, and this is a major part of my career, is to help patients get access to clinical trials and run important clinical trials that could lead to new discoveries – is this regimen better? What’s the toxicity?

Because until we have a cure for breast cancer, we need to do better, and we need to research better treatment options. So, doing trials, having access to clinical trials where you can participate, help move the science forward is key.

I think where we’re moving with breast cancer is the more we’re understanding the patient and the tumor, the more we’re realizing every single breast cancer is different, actually, and whereas when I started my training 20-plus years ago, breast cancer was breast cancer – we weren’t even using HER2 yet, we were just learning how to use estrogen receptor, and we kind of treated everything the same – now, we’re subsetting, and subsetting, and subsetting. Even in triple negative breast cancer now, which is about 18-20% of breast cancer, we’re subsetting.

Does that triple negative breast cancer have PD-L1, which is associated with being able to get immunotherapy drugs? Does it express androgen receptor? Because sometimes, even a breast cancer that doesn’t have estrogen or progesterone receptor can express the androgen receptor, like prostate cancer, and we can use some prostate cancer drugs. So, even triple negative breast cancer we’re subsetting and subsetting, and could that triple negative breast cancer be associated with a BRCA1 or 2 mutation, and then we can use the PARP inhibitors?

So, I’m actually really excited about that we’re learning more and more, and subsetting, and not treating breast cancer as one size fits all, and if we can better tailor the treatments to the patient and the tumor, that we are going to get to the point where I can tell my patients yes, we can get cures in metastatic breast cancer.

Factors that Guide a Metastatic Breast Cancer Treatment Decision

Factors that Guide a Metastatic Breast Cancer Treatment Decision from Patient Empowerment Network on Vimeo

Dr. Julie Gralow discusses factors that affect metastatic breast cancer treatment decisions, including the cancer’s biology, the overall health of the patient, and treatment side effects.

Dr. Julie Gralow is the Jill Bennett Endowed Professor of Breast Medical Oncology at the University of Washington, Fred Hutchinson Cancer Research Center, and the Seattle Cancer Care Alliance. More about this expert here.

See More From INSIST! Metastatic Breast Cancer

Related Resources:

 

What Could Metastatic Breast Cancer Genetic Testing Advances Mean for You?

What Are Essential Genetic Tests for Metastatic Breast Cancer Patients?

Metastatic Breast Cancer: Debunking Common Misconceptions

 

Transcript:

Katherine:                  

Well, Dr. Gralow, what other factors should be taken into consideration with a treatment route?

Dr. Gralow:                

I always like to think of the treatment decision as relying on three factors, and the first relates to the tumor factor, the cancer factor.

So, we talked a lot about the biology, the estrogen receptor, the HER2, the genomic profiling. So, that’s critical, but there are two other components that we need to really strongly consider when trying to devise the right treatment regimen. One of those is patient factors, and not just the patient’s genetics, but are they pre- or post-menopausal?

What is the age? Where are they in life? Are they young with young kids? Are they working, and is that an important priority for them? Are they older and with grandchildren, and they don’t need to work? What is it that would be critical? What are the patient’s priorities here, and what are their fears, what are the things they would – what would be really important as we plan a regimen? And so, the patient factors which would be patient priorities and where they are in life right now.

And then, there’s factors related to the treatment itself, which would include not just how effective it is, but – and, this is really important when trying to decide regimens – what are the side effects of a regimen? For some patients, hair loss is a big deal, and we can put it off as long as possible – maybe choosing the first couple regimens don’t cause hair loss sometimes.

But, for other people, that doesn’t matter to them. For some, we have oral – some regimens, and that could keep them out of the infusion room, and others actually – I’ve had patients who actually like coming into the infusion room regularly so that they can review the side effects and get the reassurance provided by it. So, we’ve got different route of administration of the drugs, different side effects. If you already had, for example, a neuropathy – a numbness/tingling of fingers and toes – from treatment that you might have gotten for early-stage disease, we’d probably want to avoid drugs where that’s their major side effect in the metastatic setting and that would increase that even further.

We’ve got some drugs that cause a lot of toxicity to our GI system – nausea, vomiting, or diarrhea – and other drugs that don’t. And so, understanding what symptoms the patient already has and actually tailoring the treatment based on some of the side effects of the drug could also be done, as well as how they’re administered. So, again, patient factors, tumor factors, and then, factors related to the treatment itself all come into play when we make decisions.

Katherine:                  

There have been so many advances in breast cancer research. What are you excited about in research right now?

Dr. Gralow:                

Well, every single drug that’s been approved, every single new regimen that’s been approved in breast cancer is the direct result of clinical trials, and this is a major part of my career, is to help patients get access to clinical trials and run important clinical trials that could lead to new discoveries – is this regimen better? What’s the toxicity?

Because until we have a cure for breast cancer, we need to do better, and we need to research better treatment options. So, doing trials, having access to clinical trials where you can participate, help move the science forward is key.

I think where we’re moving with breast cancer is the more we’re understanding the patient and the tumor, the more we’re realizing every single breast cancer is different, actually, and whereas when I started my training 20-plus years ago, breast cancer was breast cancer – we weren’t even using HER2 yet, we were just learning how to use estrogen receptor, and we kind of treated everything the same – now, we’re subsetting, and subsetting, and subsetting. Even in triple negative breast cancer now, which is about 18-20% of breast cancer, we’re subsetting.

Does that triple negative breast cancer have PD-L1, which is associated with being able to get immunotherapy drugs? Does it express androgen receptor? Because sometimes, even a breast cancer that doesn’t have estrogen or progesterone receptor can express the androgen receptor, like prostate cancer, and we can use some prostate cancer drugs. So, even triple negative breast cancer we’re subsetting and subsetting, and could that triple negative breast cancer be associated with a BRCA1 or 2 mutation, and then we can use the PARP inhibitors?

So, I’m actually really excited about that we’re learning more and more, and subsetting, and not treating breast cancer as one size fits all, and if we can better tailor the treatments to the patient and the tumor, that we are going to get to the point where I can tell my patients yes, we can get cures in metastatic breast cancer.

Metastatic Breast Cancer: Debunking Common Misconceptions

Metastatic Breast Cancer: Debunking Common Misconceptions from Patient Empowerment Network on Vimeo.

Dr. Julie Gralow debunks common misconceptions about metastatic breast cancer, including the metastatic diagnosis itself and why genetic tests are important. 

Dr. Julie Gralow is the Jill Bennett Endowed Professor of Breast Medical Oncology at the University of Washington, Fred Hutchinson Cancer Research Center, and the Seattle Cancer Care Alliance. More about this expert here.

See More From INSIST! Metastatic Breast Cancer

Related Resources:

How Genetic Mutations Affect Metastatic Breast Cancer Disease Progression and Prognosis

Factors That Guide a Metastatic Breast Cancer Treatment Decision

What Could Metastatic Breast Cancer Genetic Testing Advances Mean for You?

 


Transcript:

Katherine:                  

All right. Dr. Gralow, when you meet with patients, what are some of the more common misconceptions that you hear related to diagnosis?

Dr. Gralow:                

Well, I think people do confuse – especially at an early diagnosis – that the metastases, the travel to the local lymph nodes, is not the same as a metastatic breast cancer, so we spend some time talking about how it’s still curable and not considered a distant metastasis if the lymph nodes are in the armpit or up above the collarbone, and so, that’s something that we spend some time talking about.

This whole term of “metastatic recurrence” – unfortunately, when you start looking online and get your information from Dr. Google, you read right away that it’s no longer curable, and in 2020, yes, that’s true. That’s probably the most specific statement that we can make. We are not going with curative intent, which means we treat for a defined amount of time, and then all the disease goes away, and we stop treatment, and then you go on with your life, and it never comes back. That would be cure.

But, I think it’s really important to point out that much of metastatic breast cancer can be highly treatable, and what we hope to do – and certainly, at least a subset of metastatic breast cancer – we want to convert it more to what we would call a chronic disease, and so, think of it more like hypertension, high blood pressure, or diabetes. These are diseases that we generally don’t cure with treatment, but that we can control with drug therapy, which sometimes has to be adjusted, and if we don’t control it, we can get some bad complications.

So, that’s not all metastatic breast cancer, unfortunately – we can’t convert all of it to something where we can use a therapy for a long time that keeps it in check and where you have a pretty good quality of life – but we’re hoping that more and more, we’re getting targeted therapies and more specific treatments to patients so that we can convert more patients to a more chronic kind of situation.

Metastatic Breast Cancer Staging: What Patients Should Know

Metastatic Breast Cancer Staging: What Patients Should Know from Patient Empowerment Network on Vimeo.

Breast cancer expert Dr. Julie Gralow discusses metastatic breast cancer staging, including prognostic staging, breast cancer subtypes, and the meaning of metastasis.

Dr. Julie Gralow is the Jill Bennett Endowed Professor of Breast Medical Oncology at the University of Washington, Fred Hutchinson Cancer Research Center, and the Seattle Cancer Care Alliance. More about this expert here.

See More From INSIST! Metastatic Breast Cancer

Related Resources:

 

What Are Essential Genetic Tests for Metastatic Breast Cancer Patients?

Metastatic Breast Cancer: Debunking Common Misconceptions

What Could Metastatic Breast Cancer Genetic Testing Advances Mean for You?

 


Transcript:

Dr. Gralow:                

The staging of breast cancer has traditionally been by something we call anatomic staging, which has the tumor size, the number of local lymph nodes involved, and whether it has metastasized beyond the lymph nodes. So, that’s TNM – tumor, nodes, metastases. And so, that’s the classic staging, and based on combinations of those things, you can be a Stage 0 through Stage 4. Stage 0 is reserved for ductal carcinoma in situ, which is a noninvasive breast cancer that can’t generally spread beyond the breast, so that’s Stage 0, and then we go up for invasive cancer.

Interestingly, just a couple years ago, the big group that oversees the staging of cancers decided that in breast cancer, that TNM – the size, the lymph nodes, and the location beyond the lymph nodes – is not good enough anymore, so they came up with a proposal for what we call a clinical prognostic stage, which is a companion to the traditional TNM staging.

What they were getting at here was it’s not just how big your cancer is, how many lymph nodes, or whatever, it’s also at the biology of your cancer. So, this new clinical prognostic stage takes into account the estrogen and progesterone receptor of your cancer, the HER2 receptor at the grade, which is a degree of aggressiveness, and then, if your tumor qualifies, one of the newer genomic testing profiles that we use in earlier-stage breast cancer, such as the Oncotype DX 21-gene recurrence score or the MammaPrint 70-gene assay.

So, all of that goes into account now, and the whole point here is that the estrogen receptor, the HER2, the grade, and some of these genomics may actually make more difference than how many lymph nodes you have, where the cancer is, and how big it is, so it’s not just the size, but also the biology of the cancer that we’re trying to include in the new staging systems.

Katherine:                  

In this program, Dr. Gralow, we’re focusing on metastatic breast cancer. Would you explain when breast cancer is considered to have metastasized?

Dr. Gralow:                

That’s a great question because technically, if the lymph nodes in the armpit – the axillary area – are involved, that does represent spread beyond the breast, but if it stays in the local lymph node areas, it’s not technically called a metastatic or Stage 4 breast cancer. So, metastatic breast cancer would have traveled beyond the breast and those local lymph nodes, and some common sites would be to the bone, to the lungs, to the liver, less commonly – at least, up front – to the brain, and it could also travel to other lymph node groups beyond those just in the armpit and the local chest wall area as well.

Katherine:                  

What about subtypes? How are they determined?

Dr. Gralow:                

The main way that we subtype breast cancer right now is based on the expression of estrogen and progesterone receptor, the two hormone receptors, and the HER2 receptor, the human epidermal growth factor receptor. So, to date, those are the most important features when we subtype, and so, a tumor can either express estrogen and progesterone receptor or not, and it can overexpress or amplify HER2 or not, and if you think that through, you can come up with four different major subtypes, in a way, based on estrogen receptor positive or negative and HER2 positive or negative.

When all three of those are negative, we call that triple negative breast cancer, and that’s about 18-20% of all breast cancers as diagnosed in the U.S. And then, when all three are positive, we sometimes call it triple positive, and the reason that we subtype is because we know that those different subsets act differently and that we have different drugs to treat them with, and we’ve got great drugs in the categories of hormone receptor positive and HER2 positive, and increasingly, some recently hope in a new drug approval or two in triple negative breast cancer as well.

When Is a Full Mastectomy Appropriate for Metastatic Breast Cancer Patients?

When Is a Full Mastectomy Appropriate for Metastatic Breast Cancer Patients? from Patient Empowerment Network on Vimeo

Dr. Stephanie Valente discusses mastectomy for metastatic breast cancer patients, including common misconceptions around breast cancer surgery.

Dr. Stephanie Valente is the Director of the Breast Surgery Fellowship Program at Cleveland Clinic. More about this expert here.

See More From INSIST! Metastatic Breast Cancer


Transcript:

Dr. Valente:                

So, there are a lot of reasons that a woman undergoes a mastectomy. The first one is choice. So, anytime somebody is diagnosed with breast cancer, they actually have the choice of whether or not they want to remove their whole breast. So, even if their cancer is small, they do have the option of removing the whole breast. If the cancer is smaller, they might have the option to save the breast, which is called a lumpectomy.

Sometimes cancer is found, and it’s a little bit more advanced where saving the breast is not an option. So, the cancer is larger than a lumpectomy would allow. And sometimes that’s what’s called the extent of disease. So, the amount of breast tissue that’s involved requires a majority of the portion of the breast to be removed.

So, just because a woman has breast cancer that’s made its way out of the breast, into the lymph nodes, or beyond – so, metastatic cancer – doesn’t necessarily mean that she needs a mastectomy. So, just because you’ve got metastatic cancer doesn’t necessarily mean that the breast needs to be completely removed.

So, I think that one of the biggest misconceptions is that the more aggressive somebody is with their surgery, the better their chances with survival.

And again, taking a step back and saying you can choose a more aggressive surgery, but a more aggressive surgery doesn’t necessarily mean it gets you out of chemotherapy or it gets you out of radiation therapy. Those things are recommended, independent of a woman’s choice for the type of surgery that she may or may not pick.

Metastatic Breast Cancer: Accessing the Best Treatment For YOU

Metastatic Breast Cancer: Accessing the Best Treatment For YOU from Patient Empowerment Network on Vimeo.

How could genetic testing results impact your metastatic breast cancer treatment options? In this INSIST! Breast Cancer webinar, Dr. Julie Gralow discusses essential testing, the latest targeted therapies and emerging breast cancer research.

Dr. Julie Gralow is the Jill Bennett Endowed Professor of Breast Medical Oncology at the University of Washington, Fred Hutchinson Cancer Research Center, and the Seattle Cancer Care Alliance.

Download Program Resource Guide


Transcript:

Katherine:

Welcome to Insist Breast Cancer, a program focused on empowering patients to take an active role and insist on better care. Today, we’ll discuss the latest advances in metastatic breast cancer, including the role of genetic testing and how this may affect treatment options. I’m Katherine Banwell, your host for today’s program, and joining me is Dr. Julie Gralow. Welcome, Dr. Gralow. Would you introduce yourself?

Dr. Gralow:   

Hi, thanks, Katherine. I’m Dr. Julie Gralow. I’m the Jill Bennett Endowed Professor of Breast Medical Oncology at the University of Washington, Fred Hutchinson Cancer Research Center, and the Seattle Cancer Care Alliance.

Katherine:    

Excellent, thank you. Before we begin the discussion, a reminder that this program is not a substitute for seeking medical advice. Please refer to your own healthcare team. Well, Dr. Gralow, let’s start by helping people understand how breast cancer is staged. Could we go through those stages?

Dr. Gralow:     

The staging of breast cancer has traditionally been by something we call anatomic staging, which has the tumor size, the number of local lymph nodes involved, and whether it has metastasized beyond the lymph nodes. So, that’s TNM – tumor, nodes, metastases. And so, that’s the classic staging, and based on combinations of those things, you can be a Stage 0 through Stage 4. Stage 0 is reserved for ductal carcinoma in situ, which is a noninvasive breast cancer that can’t generally spread beyond the breast, so that’s Stage 0, and then we go up for invasive cancer.

Interestingly, just a couple years ago, the big group that oversees the staging of cancers decided that in breast cancer, that TNM – the size, the lymph nodes, and the location beyond the lymph nodes – is not good enough anymore, so they came up with a proposal for what we call a clinical prognostic stage, which is a companion to the traditional TNM staging.

What they were getting at here was it’s not just how big your cancer is, how many lymph nodes, or whatever, it’s also at the biology of your cancer. So, this new clinical prognostic stage takes into account the estrogen and progesterone receptor of your cancer, the HER2 receptor at the grade, which is a degree of aggressiveness, and then, if your tumor qualifies, one of the newer genomic testing profiles that we use in earlier-stage breast cancer, such as the Oncotype DX 21-gene recurrence score or the MammaPrint 70-gene assay.

So, all of that goes into account now, and the whole point here is that the estrogen receptor, the HER2, the grade, and some of these genomics may actually make more difference than how many lymph nodes you have, where the cancer is, and how big it is, so it’s not just the size, but also the biology of the cancer that we’re trying to include in the new staging systems.

Katherine:    

In this program, Dr. Gralow, we ’re focusing on metastatic breast cancer. Would you explain when breast cancer is considered to have metastasized?

Dr. Gralow:  

That’s a great question because technically, if the lymph nodes in the armpit – the axillary area – are involved, that does represent spread beyond the breast, but if it stays in the local lymph node areas, it’s not technically called a metastatic or Stage 4 breast cancer. So, metastatic breast cancer would have traveled beyond the breast and those local lymph nodes, and some common sites would be to the bone, to the lungs, to the liver, less commonly – at least, up front – to the brain, and it could also travel to other lymph node groups beyond those just in the armpit and the local chest wall area as well.

Katherine:   

What about subtypes? How are they determined?

Dr. Gralow:   

The main way that we subtype breast cancer right now is based on the expression of estrogen and progesterone receptor, the two hormone receptors, and the HER2 receptor, the human epidermal growth factor receptor. So, to date, those are the most important features when we subtype, and so, a tumor can either express estrogen and progesterone receptor or not, and it can overexpress or amplify HER2 or not, and if you think that through, you can come up with four different major subtypes, in a way, based on estrogen receptor positive or negative and HER2 positive or negative.

When all three of those are negative, we call that triple negative breast cancer, and that’s about 18-20% of all breast cancers as diagnosed in the U.S. And then, when all three are positive, we sometimes call it triple positive, and the reason that we subtype is because we know that those different subsets act differently and that we have different drugs to treat them with, and we’ve got great drugs in the categories of hormone receptor positive and HER2 positive, and increasingly, some recently hope in a new drug approval or two in triple negative breast cancer as well.

Katherine:     

For a patient to get diagnosed, what are the essential tests?

Dr. Gralow:  

So, we’re talking about metastatic breast cancer here, and in the U.S., maybe up to 10% or slightly less of breast cancer is technically Stage 4 or metastatic at diagnosis. That means at the time we first found it in the breast, it had already spread beyond. So, an important thing that we’ll do with a newly diagnosed breast cancer is especially if there are a lot of lymph nodes are involved or the patient has symptoms that might say there’s something in the bone, liver, or lung is staging.

So, we’ll use scans – maybe a CAT scan, bone scan, or PET scan – and we will look at whether the disease has gone beyond the breast and the lymph nodes, and if so, where. So, maybe 8-10% of breast cancer diagnosed in the U.S. already has some evidence that it has spread beyond the breast, but the most common way that metastatic breast cancer happens is that a patient was diagnosed possibly years and years ago, treated in the early-stage setting, and now it comes back, and that is the most common presentation for metastatic breast cancer, and sometimes that can be due to symptoms.

As I said, if it comes back in the bone, maybe that’s bone pain. If it’s in the lung, it’s a cough. There are symptoms. Sometimes, it’s because we’ve done a blood test or something and we find some changes there.

And so, when a breast cancer has recurred, it’s really important to document that it’s really breast cancer coming back, first of all, and so, if we can, we generally want a biopsy, and we want to stick a needle in it if it’s safe to do, and look and verify that it looks like breast cancer, and also, it’s really important that we repeat all those receptors that we talked about from the beginning because it can change.

So, a cancer up front 10 years ago could have been positive for estrogen receptor, but the only cells that survived – mutated, changed – were estrogen receptor negative, so what comes back could be different. So, it’s really critical to get that biopsy, repeat the estrogen/progesterone receptor and HER2, and also, in an ideal world, now that it’s 2020 and we’re moving more toward genomics, to do a full genomic profile and look for other changes and mutations that could drive our therapeutic options.

So, staging, knowing where the cancer is, getting a good baseline by understanding where it is and how big it is so that we can follow it and hopefully see that it’s responding to treatment, and then, repeating all of the biology components so that we know what the best options are for treatment are really critical.

Katherine:  

Right. How can patients advocate for a precise breast cancer diagnosis, and why is that important?

Dr. Gralow:    

Well, all those things I just mentioned are key. Knowing exactly where it is so that we can monitor it – for example, if the cancer has come back in the bones, we would add what we call a bone modifying agent, a drug like zoledronic acid or denosumab – Zometa or – which can suppress bone destruction from the cancer, but if it’s not in the bone, we wouldn’t add that.

And, we want to have a good look everywhere so that we can see if it’s responding because sometimes, the tumor can respond differently in one area than another. Also, I think it’s really important to know what your treatment options are by doing that biopsy, getting a full panel, and looking at potentially hundreds of genes that could be mutated, deleted, or amplified so that we know what our treatment options are.

And, we’re not going to use all the treatment options up front, so it’s helpful for knowing that if this treatment doesn’t work or is too toxic, what are the second-line or third-line options? So, we make sure that there’s what we call good staging up front so we know where the cancer is, and then we make sure that we’ve looked at it as best we can in 2020 with all the genomics.

That would give us the best chance of being tailored – individualized – to the tumor. Sometimes, if we can’t biopsy it, like with a needle that would go into a liver spot, then increasingly, we’re looking at what we call liquid biopsies, and that can be drawing the blood and seeing if we can find parts of the tumor, whether it be the DNA or the RNA that’s floating around in the blood, and sometimes we can get that information out of the blood as well.

Katherine: 

All right. Dr. Gralow, when you meet with patients, what are some of the more common misconceptions that you hear related to diagnosis?

Dr. Gralow:  

Well, I think people do confuse – especially at an early diagnosis – that the metastases, the travel to the local lymph nodes, is not the same as a metastatic breast cancer, so we spend some time talking about how it’s still curable and not considered a distant metastasis if the lymph nodes are in the armpit or up above the collarbone, and so, that’s something that we spend some time talking about.

This whole term of “metastatic recurrence” – unfortunately, when you start looking online and get your information from Dr. Google, you read right away that it’s no longer curable, and in 2020, yes, that’s true. That’s probably the most specific statement that we can make. We are not going with curative intent, which means we treat for a defined amount of time, and then all the disease goes away, and we stop treatment, and then you go on with your life, and it never comes back. That would be cure.

But, I think it’s really important to point out that much of metastatic breast cancer can be highly treatable, and what we hope to do – and certainly, at least a subset of metastatic breast cancer – we want to convert it more to what we would call a chronic disease, and so, think of it more like hypertension, high blood pressure, or diabetes. These are diseases that we generally don’t cure with treatment, but that we can control with drug therapy, which sometimes has to be adjusted, and if we don’t control it, we can get some bad complications.

So, that’s not all metastatic breast cancer, unfortunately – we can’t convert all of it do something where we can use a therapy for a long time that keeps it in check and where you have a pretty good quality of life – but we’re hoping that more and more, we’re getting targeted therapies and more specific treatments to patients so that we can convert more patients to a more chronic kind of situation.

Katherine:

So, it’s something that patients live with.

Dr. Gralow:  

Right.

Katherine:  

Many people are confused about genetic testing. They often think that it relates to ancestry or physical traits like hair and eye color. What’s the role of genetic testing in breast cancer?

Dr. Gralow:    

Well, you can do genetic testing of the patient’s inheritance, which is how most people think of genetic testing, and that’s actually really important and increasingly important in metastatic breast cancer to do your own inheritance. Have you inherited a gene that was associated with how your cancer developed? Because now, we actually have a class of drugs called PARP inhibitors that are approved for tumors that have a BRCA1 or BRCA2 mutation with them. Most of those mutations were inherited, but not all. Sometimes they can develop as well.

So, now, when my patient – if she didn’t previously have genetic testing for an inherited risk for breast cancer either coming from mom or dad’s side of the family, a lot of people do have that up front, especially if they’re younger at diagnosis or they have a lot of family members with breast cancer. If she didn’t have that genetic testing done previously, at the time of the metastatic occurrence, I’m going to recommend that that be done because knowing if the cancer is associated with one of these DNA repair genes – BRCA1, BRCA2, some other genes – we have a new treatment option, which is an oral pill that actually is highly effective if the tumor has a mutation in one of these.

But, we can also – so, that’s genetic testing of the patient’s own DNA, but we can also do what we call genetic testing – or genomic testing, if you will – of the genes of the cancer. What were the changes in the DNA at the gene level that caused a normal breast cell over time to develop into a cancer cell that’s now growing without responding to our body’s checks and balances? So, what were those mutations, deletions, or amplifications in the tumor itself?

So, we’ve got the patient’s genetics, we’ve got the tumor’s genetics, and both of those come into play when we’re making our best treatment recommendations and trying to understand what the right approach is.

Katherine:       

How is testing administered?

Dr. Gralow: 

So, for our inherited testing, those gene changes can be found in every cell in the body, so we can do that from a simple blood test where we just look at the blood cells. We can actually do it with our sputum and with a cheek swab, even. You can get enough of the DNA from the inside of the mouth to do that.

For a tumor’s genetics, we need some of the tumor, so that’s either done with a biopsy into the metastatic site or, as I mentioned before, increasingly, we’re exploring the potential for a liquid biopsy – so, drawing some blood and then trying to find pieces of the tumor that are shed into the blood.

Katherine:      

What advances have there been in testing?

Dr. Gralow: 

Well, it used to be – just going back a couple of years ago – that we didn’t do a lot of this genetic testing or genomic profiling of the tumor because we didn’t have many – the term is an “actionable mutation.” So, if we found something, would we do something with it? Did we have a drug we could use to do it? But, more and more and more, even in breast cancer, we’re finding actionable mutations that would drive therapy.

For example, in estrogen receptor positive breast cancer, we have a new class of targeted therapies called PI 3-kinase inhibitors – a drug called alpelisib or Piqray was approved in the last couple of years in that category – and it only is effective in estrogen receptor positive breast cancer that has a mutation in the PI 3-kinase gene. So, that would be something we’re looking for in the tumor’s genes, and actually, we need to know that there’s a mutation to even get the drug approved for treatment because it doesn’t work if you don’t have that mutation.

Increasingly, we’re finding some changes that can happen in the estrogen receptor gene and the HER2 gene, interestingly, so that you can have estrogen receptor expressed on your tumor, but over time, that tumor might develop an estrogen receptor mutation so that it stops responding to certain drugs that target the estrogen receptor.

And so, that’s called an ESR1. That’s the name of the estrogen receptor gene – an ESR1 mutation – and that would tell me probably not going to respond as well to a drug in the class we call aromatase inhibitors, but might respond better to a drug in the class that we call the selective estrogen receptor degraders like fulvestrant or Faslodex, is the name of a drug in that class.

We’re also finding that you can have what we call activating mutations in HER2, and they can be present whether the tumor overexpresses HER2 or not, and we’ve got some ongoing clinical trials looking at if the tumor doesn’t have extra HER2 on its surface – so, it doesn’t have extra HER2 protein, but at the gene level, it’s got an activated HER2 gene – we can use certain types of HER2 therapy to treat it, and we’re testing that right now in clinical trials.

So, could we even use some HER2 drugs even though technically, the tumor would be classified as HER2 negative? So, fascinating increasing information that we’re understanding, and I also mentioned before we can inherit mutations in genes such as BRCA1 and 2, but fascinatingly, the tumor can acquire those mutations. Even if we didn’t inherit a mutation, we can see mutations in the BRCA1 and 2 gene – we call those somatic as opposed to germline mutations. So, “germline” means it’s in every cell in your body, but “somatic” means the tumor somehow acquired this over time.

And so, we’ve done – we just presented some very early results of a trial, and we’re expanding this trial, looking at if you didn’t inherit a BRCA1 or 2 mutation, so technically, you don’t qualify for a PARP inhibitor, but if the tumor acquired a mutation and we can prove that with testing the tumor’s DNA, then we have seen responses from these PARP inhibitors, so that opens up another whole class of treatments, and there are other DNA repair genes that actually may be qualified as well that we can inherit or that can be acquired by the tumor.

So, more and more, we’re doing this genomic profiling, and it is leading to results that would give us possible treatment options.

Katherine:  

Dr. Gralow, the goal of this program is to provide the confidence and tool for patients to advocate for the essential tests to get best care personalized to them. Are there specific tests that patients should make sure they have?

Dr. Gralow:  

Well, there are a lot of assays out there to do this genomic profiling or genetic testing of the tumor, so I don’t promote any one. Various institutions do it and do it well, various companies do it, but I think every metastatic patient should have the tumor looked at in this kind of profiling.

I also think every metastatic patient should advocate for having a biopsy of their cancer, and if a biopsy cannot be done safely in the recurrence, then see if they could get a liquid biopsy – have blood drawn to find it. So, I think that patients should be asking about this. Sometimes, insurance won’t always cover it, and so, my job as a treating physician is to advocate for that, to do an appeal.

More and more, because we have so many actionable mutations in breast cancer now, I’m not having insurance decline, but occasionally, it does, and then it’s our job as the healthcare providers to make the case that yes, this will impact the patient, and yes, it should be covered by insurance.

Katherine:  

You’ve been referring to a number of terms. Patients may have heard the BRCA or “braca” that relate to breast cancer in genetics. Would you give us an overview of common mutations in breast cancer?

Dr. Gralow:    

So, of the mutations that we can inherit, the first two that were discovered were BRCA1 and BRCA2, and for all breast cancer – not just metastatic, but all breast cancer – we think that maybe 5-10% of breast cancer is the direct result of the inheritance of a strong gene that gives you a high – not 100%, but a high likelihood of developing breast cancer.

So, for BRCA1 and 2, these two genes are associated predominantly with breast and ovarian cancer, and if you live out your normal lifespan, you could have up to a 75-80% chance of getting one of those two cancers, and breast cancer being more common. Also, some association with some other cancers including, interestingly, prostate cancer, which we’re learning more about.

So, BRCA1 and 2 are the most common, and they tend to be found – because they have such a high association with the risk of breast and ovarian cancer, they tend to be found in families that have a lot of other breast cancers, and also breast and ovarian cancer presenting at a younger age. So, you’ve inherited a gene that leads to a high predisposition, and the cancer occurs earlier.

So, whereas the average age of diagnosis of breast cancer in the U.S. is 61-62 most commonly, in a patient who’s inherited a BRCA1 or 2 gene mutation, it’s closer to 40-42 – so, a lot younger. And then, there are a variety of other genes that can be inherited that are either much less common or have a weaker link. So, for example, there are genes called CHEK2 or PALB2, ATM, P53 – I just mention that because some of the listeners will potentially have one of those mutations or have heard it. Those are either rarer or they’re associated with a weaker chance of getting cancer.

So, those might be more commonly found in a family that doesn’t have a lot of cancer in it because a carrier – the mother or the father – and their other relatives would have maybe only a 30% chance of getting breast cancer in some cases. So, there would be a lot of carriers who don’t get cancer.

So, as I mentioned earlier, I think it’s really important – especially right now in metastatic breast cancer – that pretty much everybody, even if you didn’t have a strong family history, even if you weren’t diagnosed at a young age, get tested because if we find one of these inherited mutations, we now have some additional treatment options, especially right now, approved for BRCA1 or 2, but clinical trials going on for many of these other genes.

Katherine: 

How do these mutations affect disease progression and prognosis?

Dr. Gralow:          

So, most of the genes I’ve mentioned – in their normal state, they’re critical, actually. They’re called DNA repair genes, and their job in our life is when we accidentally make a mistake when we’re replicating our DNA and two cells are dividing, if there’s a mistake in the DNA, they go in and repair it. And, we’ve got all kinds of mechanisms to try to prevent mutations from happening as cells divide, and BRCA1 and 2 are a key part of that, and so, they’re fixing it.

So, if you inherit a mutation in one of those genes, you still have some ability to repair any routine mistakes that are being made, but over time, you have less ability, and then, if you get a cancer that has a deficiency in BRCA1 or 2, those cancers can be more sensitive to certain kinds of chemotherapy that affects DNA repair.

So, for example a class of chemotherapy agents called the platinum drugs – carboplatin and cisplatin – may be more effective in BRCA1- or 2-mutated cancers, also more generally in triple negative breast cancer because they can be more similar to BRCA1-mutated cancers in a lot of ways.

So, to go back to your original question, once a cancer has developed in a patient who has a BRCA1 or 2 mutation, we treat that cancer for what it is. So, it might have developed estrogen – have estrogen receptor on the surface or HER2, so we treat it as the subtype that developed, and actually, the chance of cure is just the same for BRCA1-associated breast cancer as it would be for one that doesn’t have a BRCA.

But, the chance of getting a second breast cancer – a totally new breast cancer – would be higher unless you chose to remove both of your breasts and the bulk of your breast tissue. So, decisions like surgery – if you had a known BRCA1 mutation, we’d treat the cancer you have now aggressively and for cure, but when you talk about your surgery options, we’d say doing more aggressive surgery, like removing both of your breasts – that’s not gonna improve your chance of surviving the cancer you have now, but it will markedly reduce the chance of getting a second breast cancer.

So, you could consider that as an option for surgery – not to improve your chance of this cancer, but to reduce the chance of another breast cancer. So, your surgery decisions might be impacted by knowing your BRCA1 or 2 mutation. And then, clearly, if you had metastatic breast cancer, knowing if you had the option of a PARP inhibitor, one of the drugs in that class could be – you could have a different treatment option for drug therapy.

Katherine: 

Well, Dr. Gralow, what other factors should be taken into consideration with a treatment route?

Dr. Gralow:   

I always like to think of the treatment decision as relying on three factors, and the first relates to the tumor factor, the cancer factor.

So, we talked a lot about the biology, the estrogen receptor, the HER2, the genomic profiling. So, that’s critical, but there are two other components that we need to really strongly consider when trying to devise the right treatment regimen. One of those is patient factors, and not just the patient’s genetics, but are they pre- or post-menopausal?

What is the age? Where are they in life? Are they young with young kids? Are they working, and is that an important priority for them? Are they older and with grandchildren, and they don’t need to work? What is it that would be critical? What are the patient’s priorities here, and what are their fears, what are the things they would – what would be really important as we plan a regimen? And so, the patient factors which would be patient priorities and where they are in life right now.

And then, there’s factors related to the treatment itself, which would include not just how effective it is, but – and, this is really important when trying to decide regimens – what are the side effects of a regimen? For some patients, hair loss is a big deal, and we can put it off as long as possible – maybe choosing the first couple regimens don’t cause hair loss sometimes.

But, for other people, that doesn’t matter to them. For some, we have oral – some regimens, and that could keep them out of the infusion room, and others actually – I’ve had patients who actually like coming into the infusion room regularly so that they can review the side effects and get the reassurance provided by it. So, we’ve got different route of administration of the drugs, different side effects. If you already had, for example, a neuropathy – a numbness/tingling of fingers and toes – from treatment that you might have gotten for early-stage disease, we’d probably want to avoid drugs where that’s their major side effect in the metastatic setting and that would increase that even further.

We’ve got some drugs that cause a lot of toxicity to our GI system – nausea, vomiting, or diarrhea – and other drugs that don’t. And so, understanding what symptoms the patient already has and actually tailoring the treatment based on some of the side effects of the drug could also be done, as well as how they’re administered. So, again, patient factors, tumor factors, and then, factors related to the treatment itself all come into play when we make decisions.

Katherine:    

There have been so many advances in breast cancer research. What are you excited about in research right now?

Dr. Gralow: 

Well, every single drug that’s been approved, every single new regimen that’s been approved in breast cancer is the direct result of clinical trials, and this is a major part of my career, is to help patients get access to clinical trials and run important clinical trials that could lead to new discoveries – is this regimen better? What’s the toxicity?

Because until we have a cure for breast cancer, we need to do better, and we need to research better treatment options. So, doing trials, having access to clinical trials where you can participate, help move the science forward is key.

I think where we’re moving with breast cancer is the more we’re understanding the patient and the tumor, the more we’re realizing every single breast cancer is different, actually, and whereas when I started my training 20-plus years ago, breast cancer was breast cancer – we weren’t even using HER2 yet, we were just learning how to use estrogen receptor, and we kind of treated everything the same – now, we’re subsetting, and subsetting, and subsetting. Even in triple negative breast cancer now, which is about 18-20% of breast cancer, we’re subsetting.

Does that triple negative breast cancer have PD-L1, which is associated with being able to get immunotherapy drugs? Does it express androgen receptor? Because sometimes, even a breast cancer that doesn’t have estrogen or progesterone receptor can express the androgen receptor, like prostate cancer, and we can use some prostate cancer drugs. So, even triple negative breast cancer we’re subsetting and subsetting, and could that triple negative breast cancer be associated with a BRCA1 or 2 mutation, and then we can use the PARP inhibitors?

So, I’m actually really excited about that we’re learning more and more, and subsetting, and not treating breast cancer as one size fits all, and if we can better tailor the treatments to the patient and the tumor, that we are going to get to the point where I can tell my patients yes, we can get cures in metastatic breast cancer.

Katherine:    

For patients who may be hesitant to speak up – to advocate for themselves in the process – I’m gonna start again. For patients who may be hesitant to speak out for themselves and advocate for their own care and treatment, what advice do you have?

Dr. Gralow:   

You have a whole team who’s behind you, and I’m the MD on the team, but I’ve got a nurse practitioner, and a nurse, and a scheduler, and a social worker, and a nutritionist, and a physical therapy team, and financial counselors. I’ve got a whole team who works with me. And so, a patient might be hesitant to speak up during the actual appointment with their physician. It’s a short amount of time. I would recommend come into it with written-down questions because things go fast. You don’t get a lot of time with your doctor.

Things go fast, but don’t come in with 25 questions, either. Pick your top few that you want to get taken care of this visit because if you come in with 25 or 30, you’re gonna lose the answers to most of them. Maybe bring somebody with you who’s an advocate and a listener for you who could be taking notes, so you can process and you don’t have to write it down, or ask if you can record it. It’s really important if you’re newly diagnosed or maybe there’s a progression and you’re going on a new treatment. That’s okay too.

But, I would also say you have a whole team behind you, so sometimes, if you don’t have time or if you’re hesitant to speak up in your doctor’s visit, you can ask the nurse, or maybe you can ask the social worker for help, even. See if there’s support groups around.

Interestingly, we’ve got a peer-to-peer network where patients can request to talk to somebody else who’s matched to them by some tumor features, and their stage, and things like that. Maybe finding somebody else who’s gone through something similar, and somebody independent to talk to instead of relying on your family.

It can also be really helpful to talk to a therapist or a psychologist about your fears, and sometimes, you want to be strong for your family, strong for your children and all, but you need a safe space with somebody that you can just express your fears and your anger if that’s what’s going on, or your depression or anxiety to while you’re trying to hold a strong face for others in your family. So, I would encourage patients to look at who is the whole team and talk to the other members of the team as well, and sometimes, they can help advocate.

Also, find somebody who might be able to come to your appointments with you, somebody who will help you advocate or remind you – “Didn’t you want to ask this question?” – or be another set of ears that you can process it with afterwards.

Katherine:     

Dr. Gralow, we’ve covered a lot of useful information today for patients. Thank you so much for joining us.

Dr. Gralow:    

Thank you, Katherine.

Katherine:       

And, thank you to all of our partners. To learn more about breast cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell.

Does Cannabis Oil Have a Role in Cancer Treatment?

Does Cannabis Oil Have a Role in Cancer Treatment? from Patient Empowerment Network on Vimeo.

Is it just a trend or could cannabis oil truly have a role in cancer care and treatment? Dr. Sangmin Lee share his perspective.

Dr. Sangmin Lee is a hematologist-oncologist specializing in blood disorders and blood cancers at Weill Cornell Medicine and New York Presbyterian Hospital. More about Dr. Lee here.

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Transcript:

Patricia:

The use of cannabis oil is becoming prevalent. Does this have a role in cancer care and treatment?

Dr. Lee:

Absolutely. So, we use it for a lot of side effect management. So, cannabis can be helpful, in terms of appetite and nausea, for example. So, we often use it in conjunction to manage some of the side effects that patients can have throughout their treatment.

You should consult with your medical team, and of course, I should say that laws differ state by state, so it doesn’t apply to every state. But when it’s available, it can be a valuable addition.

Patricia:

Sure. Discuss that with your physician.

Are Clinical Trial Participants Monitored More Closely?

Are Clinical Trial Participants Monitored More Closely? from Patient Empowerment Network on Vimeo.

Dr. Sangmin Lee discusses the monitoring of clinical trial participants and the measures taken for patient safety.

Dr. Sangmin Lee is a hematologist-oncologist specializing in blood disorders and blood cancers at Weill Cornell Medicine and New York Presbyterian Hospital. More about Dr. Lee here.

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Transcript:

Patricia:

How about this next one? I am monitored more closely in a clinical trial.

Dr. Lee:

In some cases, it’s true. Clinical trials do have certain monitoring visits, in terms of doctor’s visits, laboratory tests, and physical exams.

The purpose of that is to make sure that it is safe. So, the purpose of monitoring closely, in a lot of cases, is for the patient’s safety. We are testing drugs in a lot of clinical trials, for which the complete safety profile, as well as efficacy profile, is not known. So, the purpose of closer monitoring is to make sure whatever we’re doing is safe, and if there are any unexpected side effects, then it allows us to address the side effects, as well. So, it’s mainly for patients’ safety.

Will Clinical Trials Cost You? The Facts.

Will Clinical Trials Cost You? The Facts. from Patient Empowerment Network on Vimeo.

Dr. Sangmin Lee reviews the financial impact associated with clinical trials, including a discussion of what expenses are covered for participants.

Dr. Sangmin Lee is a hematologist-oncologist specializing in blood disorders and blood cancers at Weill Cornell Medicine and New York Presbyterian Hospital. More about Dr. Lee here.

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Transcript:

Patricia:

All right, how about this one: I may have unexpected costs if I join a clinical trial.

Dr. Lee:

So, typically, that’s actually, usually not true, because how it works is that the clinical trial drugs, and that there may be extra procedures or visits associated with clinical trials.

And what usually happens is that the sponsor of the clinical trial provides the cost of the drug, intervention, and anything extra that are required for the clinical trial. So, in the end, the cost of participating in a clinical trial should not be any more than receiving standard care treatment.

In some rare cases, there may be stipends associated with the clinical trial, especially with travel. So, if you participate in a clinical trial, and you live far away, then you should ask to see if there is any stipends available, especially for travel.

Is It Safe? Breaking Down the Clinical Trial Process

Is It Safe? Breaking Down the Clinical Trial Process from Patient Empowerment Network on Vimeo.

The idea of a clinical trial can be intimidating and confusing for many patients. Dr. Sangmin Lee explains the phases of clinical trials, including the safety protocols in place to protect patients.

Dr. Sangmin Lee is a hematologist-oncologist specializing in blood disorders and blood cancers at Weill Cornell Medicine and New York Presbyterian Hospital. More about Dr. Lee here.

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Transcript:

Patricia:

What is the process for getting medicine to patients during clinical trials?

Dr. Lee:

So, clinical trials are basically what’s needed to prove that drugs work. So, a lot of times, we test drugs in a test tube in AML cell lines, and they show great promise. But just because a drug works in a test tube setting, doesn’t actually mean that it will work in humans, because human bodies are much more complicated. So, we need to test promising drugs in humans to make sure they are safe and effective.

And that’s what the purpose of clinical trials are. Once they demonstrate safety and efficacy, then a drug then gets to be approved, and is available commercially. So, that’s the purpose of clinical trials.

To be involved in clinical trials, what it involves is, basically, you have to meet a sort of criteria, called eligibility, because different clinical trials have different criteria for selection. So, we have to look into that. And then, once you fit an eligibility or selection criteria, then you typically undergo certain diagnostic tests to enroll on a clinical study. And then, you get whatever drug or intervention that is designed to test in that setting.

So, there are numerous steps to actually enroll in a clinical study.

Patricia:

And like you mentioned, there’s a long way between rat studies and human trials. What are the phases of clinical trials?

Dr. Lee:

So, there are three phases for clinical trials, commonly. There’s phase one, and phase two, and phase three. Phase one is the earliest part of the clinical trial process. So, goal of a phase one study is to make sure a drug is safe in a human. So, phase one studies are usually the first time that you are testing the drug in humans, and the main purpose is to demonstrate that it’s safe. So, typically, in a phase one study, typically, you test a drug at a lower dose or dose levels to demonstrate safety. What it means is that you’re enrolling a few patients at a time.

Once a drug is proven to be safe, then you move on to phase two, which is basically testing the drug in more patients. And the purpose of phase two is to get a preliminary assessment of how effective a treatment would be.

So, typically, a phase two study involves many more patients in that setting. And then, if a phase two study shows that a drug is very promising, then the drug may move on to phase three, where, basically, in phrase three, you are comparing one intervention or a drug compared to the standard of care. And, typically, in a phase three setting, a computer decides randomly which intervention you get, whether it’s an intervention or new drug versus standard of care. And standard of care may include either placebo or chemotherapy intervention, that is standard of care. So, it’s not always placebo in phase three.

Breast Cancer Before 40: What You Should Know

Breast Cancer Before 40: What You Should Know from Patient Empowerment Network on Vimeo.

Dr. Stephanie Valente reviews key information for women under the age of 40 with breast cancer, including risk, treatment approaches and the role of genetic testing.

Dr. Stephanie Valente is the Director of the Breast Surgery Fellowship Program at Cleveland Clinic. More about this expert here.

Related Program:

Breast Cancer Before 40: How Can I Preserve My Fertility?


Transcript:

Sure. So, when we talk about breast cancer in young women, usually we are referring to women under the age of 40. And the prevalence for breast cancer in general is one out of eight women. For women under the age of 40, it’s about a seven percent incidence of breast cancer. So, it’s about a seven percent incidence in the general population in the United States. So, that’s about 12,500 women per year are diagnosed under the age of 40 with breast cancer.

So, the prevalence has pretty much been the same over the years. We used to think that women diagnosed at a younger age had a more aggressive breast cancer. But the more we look at things, the more we realize that women under the age of 40 usually are diagnosed at a later stage because it’s not something that somebody in their 20s or 30s is thinking that a breast lump equates to cancer. So, these women unfortunately present at a later stage.

Many times, it’s because they are pregnant, breastfeeding or just not having any family history where the first thing they think of when they get a lump is that they actually have breast cancer.

So, the first thing is women under the age of 40 usually present at a later stage, meaning that they have larger cancers, and the cancers because they are larger have had more time to spread to the lymph nodes. So, these women they don’t necessarily have more aggressive breast cancers than older women, it’s just that it’s found at a later stage.

So, the treatment options are the same for young women with breast cancer. So, depending on the size of the tumor and the size of her breast, women are given the option for a lumpectomy which usually is follow by radiation versus a mastectomy. And studies have shown that either surgical choice is a good option for women. And that one surgery doesn’t make a young woman, or an older woman live any longer.

That the survival for breast cancer is based on stage not the choice of surgery that they pick.

So, one of the first things is that women under the age of 50 – the average age for breast cancer in the United States is between 64 and 68.

So, if you are under the age of 50 or under the age of 40 there’s a higher chance that maybe these women carry a gene that would increase the risk of getting breast cancer. And so nowadays, we test over 21 genes. But these genes can increase their risk of getting breast cancer not only in the breast they have the breast cancer in, but in their other breast as well. It also increases the risk for other types of cancers such as ovarian cancer. And they could potentially pass this gene on to their kids.

So, sometimes women – and this is the great thing about academic medicine. Everything is changing so quickly with the modern research. So, a lot of times a woman who is triple negative, which is an estrogen receptor negative breast cancer.

If they are genetic positive for the BRCA gene, they qualify for certain medications or chemotherapy that we know targets specifically that type of cancer and their gene. So, that’s why it is important for some of these women to get genetic testing to see if the certain chemotherapy regimens or medicines that we have would benefit their type of cancer.

So, one of the things for any woman diagnosed with breast cancer at a young age is to offer those women genetic testing. And sometimes it can be a relief or sometimes it can be very challenging for these women to think, “Oh my gosh. I have this gene. I’m at increased risk for more cancers.” And that potentially they could pass that on to their children.

So, having the women who come in meet with a genetics counselor to go over the risks. And the reality is that of all the women under the age of 50 that test for the gene, only 10 percent actually carry the gene.

So, the good thing is that 90 percent most likely don’t have the gene. But it still is an anxiety provoking thing for these women to go through.

Another thing is that these women a lot of times are younger. So, they have either two things – young children to take care of which is extremely difficult to mange an already stressful motherhood. You throw in a diagnosis of cancer, whether or not there is a dad involved or a father that needs to help out with these kids. A lot of times their families need to help out. So, we have a psych oncologist that’s part of our team. And it’s really great. How do you tell your kids you have cancer? And how do you manage kind of day-to-day life with going through this? So, that’s another great program that is offered. And importantly for a woman who doesn’t have children but maybe desires to have children or even to have more children than the ones that she has,
looking at fertility options for young women is huge.

So, we know that some of the chemotherapy that we give breast cancer patients decreases their ability to have children in the future. So, the chemotherapy can shut down the ovaries. So, sometimes women – and this is the great thing about academic
medicine. Everything is changing so quickly with the modern research. So, a lot of times a woman who is triple negative, which is an estrogen receptor negative breast cancer.

If they are genetic positive for the BRCA gene, they qualify for certain medications or chemotherapy that we know targets specifically that type of cancer and their gene. So, that’s why it is important for some of these women to get genetic testing to see if the certain chemotherapy regimens or medicines that we have would benefit their type of cancer.

So, the one thing is that I tell these women that breast cancer takes a good year between chemotherapy if they need it, surgery, radiation of they need it and the whole process of recovery. That is really takes a good solid year before they are kind of done going to their doctor’s appointments. But the reality is that for an early stage breast cancer, studies have show for young women the overall survival is over 92 percent. So, I say, “This is going to be a tough year. We are going to get through this together. And the good thing is that you are going to be alive in five, 10, 15, 20 years. And so, our goal is to get you the best quality of life not only now but in the future.”

As far as hope for young women with breast cancer, things are changing so fast. The medicine that’s out there – we’re doing these studies where women are getting chemotherapy and by the time they get to surgery about 40 to 60 percent of the tissue that I take out has no residual cancer. That’s phenomenal. That means that the medications that these women are getting are working really well for their cancer. And so, the hope is that in 10 years I don’t have a job because the medicine that they are getting works so well that the cancer can be removed without needing surgery. And so, I think in our lifetime we will find either a cure or a complete resolution of breast cancer.

Is It Difficult to Participate in a Clinical Trial?

Clinical Trial Mythbusters

Clinical Trial Mythbusters: Is It Difficult to Participate in a Clinical Trial? from Patient Empowerment Network on Vimeo.

Downloadable Program Guide

Three experts discuss the clinical trial process and the difficulty in participating in a trial. Our expert panel includes:

  • Ken Getz, MBA – Founder and Board Chair, CISCRP
  • Andy Lee – Senior Vice President and Head, Global Clinical Trial Operations, Merck
  • T.J. Sharpe – Melanoma Survivor and Patient Advocate

Transcript:

Andrew Schorr:

And greetings from Southern California. I’m Andrew Schorr from Patient Power. And welcome to this Patient Empowerment Network program, another in our series of Clinical Trials MythBusters. Our goal, of course, is to help you get the treatment for you or a loved one that you need and deserve. I want to thank the financial supporters for this program to the Patient Empowerment Network; AbbVie, Inc., Celgene Corporation. Daiichi Sankyo and Novartis for their support. They have no editorial control and we’re going to have a very freewheeling discussion today. And really what it’s about is how can a clinical trial be made easier for you to participate? Are there barriers? We’ve talked about it in previous programs. But specifically, what are the companies—the pharmaceutical industry mostly, who sponsor trials all around the world, what are they doing to make trial participation easier? For you to know about trials. For the people at your clinic to know about it and what to say and how to administer it. For you to have documents that are understandable for you and your family to know whether you want to participate. To keep you informed. And also related to the requirements of trials. How can they be relaxed a little so that there may be a trial that would benefit you, that you and your doctor agree on, and the requirements of it allow you to be in the trial. Okay, and the logistics of it are not so tough either. All right, I’ve been in two clinical trials, and I believe I’m alive today because of that. So, I’m very grateful. We have some wonderful panelists with us over the next hour. Now as you have questions, send them to questions@patientpower.info. And some of you have. So, you’ll be able to interact with us as we go along. First, I want to go to Ft. Lauderdale, Florida, and T.J Sharpe. And T.J. has been on programs with me over the years. Stage four melanoma patient having been in trials. And T. J., you would agree, you’re alive today because you were in trials, right?

T.J. Sharpe:

Absolutely, Andrew. I think both of us are very fortunate that we found a trial that was the right treatment for us and gave us the ability to combat our disease in areas may not have been available to us if we just waited for standard of care therapies.

Andrew Schorr:

Right. And here you are—we should say that you were diagnosed a number of years ago with melanoma, went through trials. And now you’ve had two years without treatment, right?

T.J. Sharpe:

Yes. It’s been five years of treatment followed by now two good years of a clean bill of health.

Andrew Schorr:

Well, great. And I should mention for our audience, many people are familiar with T.J. T.J. goes around the country, gives speeches. He’s been at many events, consults with industry that are developing trials to try to bring the patient perspective forward. So, T.J., thank you for all you do. We really appreciate it.

T.J. Sharpe:

You’re welcome. It’s my honor to be able to represent all these patients.

Andrew Schorr:
Well, most every family—certainly most have been touched by cancer. But our other guests are not cancer patients but are in national leadership programs. And so, let’s go up to Medford, Massachusetts at Tufts University outside Boston, Ken Getz. Ken, welcome to the program. Ken, ladies and gentlemen, is a true national leader when it comes to clinical trials and really helping us move forward with better processes, better understanding. Ken, tell us a little bit about your organization there, CISCRP. What does that stand for?

Ken Getz:

Thank you. And I have to say your pronunciation was nearly perfect. It’s hard to pronounce it. It’s an acronym and it stands for The Center for Information and Study on Clinical Research Participation. It’s a non-profit organization. It was founded 18 years ago. And it’s really there to help patients and their families navigate the whole clinical research progress which for many is completely unfamiliar terrain until they’ve been diagnosed with an illness or when they have exhausted all other treatment options. So, CISCRP really helps people become more educated and informed so that they can really think of the clinical research process with more confidence. And they can navigate this unknown terrain.

Andrew Schorr:

All right. I’m going to come back to you in a minute because you have such an overview, and you’re also an Associate Professor at Tufts. And so, you study all this, and you’ve written books. But I want to introduce the third guest. And that is a leader from the pharmaceutical industry and one of our most respected and venerable companies in the field, and this is Merck. So, joining us in a senior vice president of clinical operations there around the world. And that’s Andy Lee. Andy, welcome. Thank you so much for being with us.

Andy Lee:

Andrew, thank you. And pleasure to be with some prestigious panelists, both of whom I know. And I’ve met you over the last two weeks. And thank you to T.J. and yourself who have been trial participants and who are representing that part of the organization.

Andrew Schorr:

Okay, and we should mention that both T.J. and Andy are working on a couple of levels. And Ken sounds off on this too. There is a group called TransCelerate where pharmaceutical industry is working together on some of the issues they face in having the proliferation of trials. More trials sites, more accessibility, procedures for that. And then, of course, Andy has helped lead that effort at Merck related to breakthrough therapies that they have been trying to develop there in supporting patients who might be in Merck trials. So, we are going to come back to that. But I want to go to you for a second, Ken. Ken, how low is the participation among adults in clinical trials, at least in the U.S. Now, I’ve heard really low percentages. Where are we now with that?

Ken Getz:

Right, it’s a great myth for us to start with, this notion that only three to five percent of patients—eligible patients, participate in clinical research. That’s actually a statistic that was published by the National Cancer Institute in the early 1990’s. The latest research really shows that it varies widely. For example, when we look at pediatric cancers, the participation rates are extremely high, 80 to 90 percent in same cases—pediatric leukemia. In part because those communities have very engaged healthcare providers, very engaged families that really share their information. It’s just an enabled community where all of the stakeholders support participation. And then there are other areas of course. Some cancers where we do see relatively low participation rates. But I want to point out that low participation is driven by so many factors, Andy, including the strict eligibility criteria. And the demanding protocol designs which are a real burden for some people, and they choose not to participate. As well as low awareness, very low accessibility to trials among minorities and underserved communities. So, there are many factors that contribute to this variation in the participation rates.

Andrew Schorr:

Yeah, you’ve ticked off some now. T.J., in your own experience, one of the breakthrough trials you were in you had to go from Ft. Lauderdale in South Florida and move your whole family to Tampa in central Florida, right. I mean that was a big deal.

T.J. Sharpe:

Absolutely. When you have a young family and a stage four cancer diagnosis, relocating simply across the state during the holidays especially, is no big deal. We were fortunate because we had the means to be able to move there with work situation, with family. But too many people can barely go across the county, much less the state or the country to find a trial that might be the best match for them.

Andrew Schorr:

Andy, so we’ve ticked off some of the obstacles, and Ken touched on some about even the proliferation of trials. Is that a lot of what you do is how can we have trials be more accessible, be more widely distributed to a clinic near you?

Andy Lee:

Yes, let me just explain. When we look at a new cancer therapy, we look at the various cancers that may be affected. And what we do is we go for high probabilities of success. And the challenge is if you bring a new cancer agent. You normally start off in very advanced disease. So, patients would have failed multiple lines of therapy, and often it is a last gasp. And you have to show some sort of clinical efficacy. And then you move sort of backwards in the disease, and you go from sort of third-plus line, second line and first line.

And then you may work downwards into earlier stages of the disease into an adjuvant setting and maybe a neoadjuvant setting. So, as we sit down and design a trial, what we need to look at is what is the population that is most likely to show any benefit at all. And quite often when you are developing a new therapy, it’s difficult to show benefit because many of the patients are very ill. So, what we have to do is optimize the opportunity for success of a compound by going to the right target patients.

And quite often as we have learned a lot more about cancer, this does not mean we test a product broadly in anyone with cancer. We typically try and find a profile of a patient that is likely to respond. And many patients now will realize their predictor biomarkers or prognostic biomarkers. So, for example, with immunotherapies, those that work through the PD1 mechanism would probably want to have a PD1 ligand receptor positive patient who is likely to bind to the drug.

And that gives a higher probability of success. So, it sounds counterintuitive that while we want to develop therapies for all cancer patients, when we start clinical trial development, we have to show efficacy in a population that will benefit. And that’s normally predefined and makes the inclusion criteria fairly strict. As we show efficacy and as we can move into broader populations, it makes it a lot easier for us to design more liberal clinical trials. And then we can actually spread those in the geographic domains.

I could talk more about geographic allocation, but let’s hold that for the time being, and let’s see if there’s time later on.

Ken Getz:

Can I just add to what Andy said because I think it’s really important for your viewers to understand just how active drug development activity is today. We’re looking at over 4,000 pharmaceutical and biotechnology companies, some of them very, very small. But in total, we’re looking at nearly 6,000 drugs that are in active clinical trials. And to Andy’s point, many are really targeting a patient with a very specific genetic profile or a specific biomarker. But it should give anyone who believes that a clinical trial may be an important care option for them, they should recognize that there may be many, many trials out there.

In total we estimate as many as 80,000 clinical trials, nearly 50 just conducted in the U.S. alone—50,000. So, it’s just important that we keep all this activity in perspective.

Andrew Schorr:
Right. So, T.J., that’s why all of us as patients need to ask about them, right? Go to different resources, whether it’s an advocacy group that you ultimately spoke with other patients, and obviously quizzing the doctors we go to. Is there something that may line up with my situation, right T.J.?

T.J. Sharpe:

Absolutely. There is a both top down and bottom up approach here that patients as they become educated—and every patient should be the owner of their healthcare as they become educated. Hopefully they are coming across advocacy organizations, other informed patients, patient support groups—all of which will help inform them different options for disease treatment, including hopefully as Ken mentioned, clinical research as a care option. At the same time, there is certainly very much an opportunity from the top down from the sponsors who develop the trials and from the sites that execute them to educate patients as they come in.

Not just at their own site, but at any site, at any medical facility. That if you have a diagnosis and you are looking into your care options, that you should be asking the question. And we should be giving you more information on the possibility of clinical trials and where you may find clinical trials that are appropriate for you.

Andrew Schorr:

Right, the whole enchilada, if you will, of all your options. Andy, so you mentioned about trial requirements. So, first of all, what efforts either at Merck or are you aware in the industry are being made to really talk to patients early on as you are designing trials? Whether it’s the requirements—how many CT scans you’re going to have. How often you are going to have to go to the main trial site. All the different things that sometimes get in the way.

Andy Lee:

Well, firstly we start with design. And we believe in exquisite trial design, quality by design as well. So, what we want is to run the experiment once and not have a sloppy trial design. We want to make it really robust in terms of scientific integrity and operational execution. So, we have a lot of internal design committees and what we do is we co-op with many groups external to our company. So, we speak to people who run clinical trials at cancer institutes.

We speak to the doctors who manage this. We speak to the trial coordinators. We speak to people involved with the transporting and shipping of medicine how they would do that. And then we of course speak to people in the ecosystem. We quite often speak to investigational review boards before we start trials. We talk to them about our design and what would be best to protect the rights and well-being of patients. And then, of course, the patient-centric approach says that we need patient insights.

And I’ve chosen my words very carefully because the insights are really important. Not all patients—and I’m very respectful that some patients are very intelligent and actually may be involved in this. Some patients can contribute to design, not all can. And so, what we do is we take the insights and we impute those. We often have focus groups. We talk about this disease. We talk about the burden of the disease. And then we talk about how that disease is managed in an ecosystem. And quite often in different countries it’s managed differently.

And so, we have to appreciate the global clinical trials have to navigate a path that may not be a linear path as we’d see it at an exquisite elite cancer center in the United States. It’s community-based, it’s all the rest. So, we take that input, and what we try to do is unburden the trial for the patient. We say, “How can we design a trial that requires the least visits to the clinic—the hospital, the least burden for them. And how can we take some of that burden from the clinic and actually transfer that into an easier environment.

So, document reading and review. Perhaps filling in questionnaires about quality of life. These are things that don’t have to be done in the clinic itself. And then often when we work with clinics, we work with them to help them understand how we as sponsors can make their life easier. And some of those things might be simplifying the informed consent. But I want to stress just one point here is that we can do whatever we like in the design at a company.

One of the things is, the patients are not sponsor patients. Okay, we sponsor clinical trials. The patients are managed by a doctor and a professional. And underneath that principal investigator is a whole oncology team. And it involves radiology. It involves pharmacists. It revolves around a 360 multidisciplinary team. They’re exquisite. They help manage the patient, not the sponsor. We provide the enabling functions for them. And then also that the oversight of the patient’s right, safety and wellbeing is the responsibility of an institutional review board.

And while we may provide templates and simplify templates in text and language, we rely heavily on the institutional review boards to help us with things that may make things easier, such as reimbursement for parking, transport, all of these things. And by and large, the institutional review boards are very supportive of these things. But they are very difficult to quantify in exact terms because of different geographic regions and different norms in different places. So, we rely heavily on exquisitely well-trained 360 team who manages oncology patients with a great PI. They manage patients.

And we work collaboratively with the sites who work with patients on our behalf. So, I just wanted to say the myth is that sponsors interactive with patients. That’s a myth. And the truth is that we engage with clinical sites, and we try and make our design and all the elements—the enabling elements, simpler for the trial sites in order to manage the patients in a simpler way.

Andrew Schorr:

Okay. Thank you for that. So, Ken, I want your comment on that. Because okay, we are downstream patients. We have a doctor, healthcare team. And we know somewhere in the background there’s a sponsor that tried to enable good things to happen to get reliable data and hopefully a cure for us. So, how do we—what’s happening? Are we improving things there in that interaction between clinic and patient?

Ken Getz:

Yes, we absolutely are. And I’ll start by just echoing and acknowledging that Andy has really laid out just an incredible amount of input that goes into the design of a protocol. And that’s really for a really large company. We see many, many examples now of patient advocacy groups or smaller companies turning to a variety of approaches to solicit input from patients and healthcare providers. Some virtual approaches through a social media or digital community. So, there’s lots of ways that feedback is being channeled.

And that’s really important. The flip side, to really answer your question, is that our protocol designs are becoming more and more complex, more and more demanding. A much larger proportion of drugs are now targeting rare diseases that have been stricter inclusion and exclusion criteria. And the designs of the studies—the number of procedures and the number of visits. The number of investigators that are involved, all of that has also continued to grow. And as a result, we do see that our trials are taking longer.

We have yet to see a year when we actually witnessed a reduction in the cycle time to conduct a clinical trial. And we just have to figure out new ways of making the participation process less burdensome and more efficient.

Andrew Schorr:

Oh, my. So, T.J., you had been living with stage four melanoma, a life-threatening condition. We have people even on our team who are living with stage four disease. So, when Ken talks about things slowing, that’s not what we want to hear. We want to hear two things. One is, we can accelerate a development of new medicine. And ideally—because this is an issue certainly in the U.S., but I think worldwide, that by speeding the process, cutting through red tape, improving procedures and us participating, the cost can be less as well.

And when we talk about cancer, the costs are going through the roof as you know for people living with chronic cancer. And you know so well, Andy, people who are on some of the medicines that you’ve come out with at Merck. Where people used to die unfortunately in short order, are living a much longer life thanks to new medicines. We want it to happen faster and be financially achievable. Andy, any comment about the pace of science?

Andy Lee:

Yeah, I would like to make a couple of comments about that. We often hear the sort of story that 80 percent of clinical trials don’t recruit on time, et cetera. We do immense feasibility. Once we have designed a protocol, we send it out to all of the countries that could potentially work with us. We have staff in 47 countries. And they look at two areas of interest. One is the medical durability, is the comparator the one we use in our country. Is the protocol designed the way we practice clinical medicine, not clinical research medicine?

And will that enable us to recruit the patients? That’s the first level. The second level we look at is to ask the question, is this operationally feasible? Can we source the comparator? Do the clinical sites have the equipment? How would we have to ship the biological samples around the world? And based on medical durability and the operational durability, we do a site selection. And we run the indicators through a Monte Carlo simulation. And we simulate this trial. What if we took three countries out? What if we added this more sites? What if we changed this inclusion?

And we come up with a model of what the recruitment would look like. And recruit about 80 percent of our trials according to our model. So, about 80 percent of our trials recruit on our model time. And then if we look at the typical time for drug development, it has been from eight to 10 years for many years in the industry. And when we look at some of the development timelines now—the cycle times. Pembrolizumab (Keytruda), for example, from first study until first approval, was 60 percent reduction in time.

We were looking in the four-year time period. And we are looking at five or six years for many indications. And so, we’ve halved that cycle time for some of the newer oncology products. And there are a number of reasons we’ve done that. One is we have found operational efficiencies. Two is the trial design has enabled us to interim analysis with independent data monitoring committees to assist with that. I’d also like to put in a positive plug for the regulators.

I do believe—and I’ll talk specifically about the FDA, because they are the agency for the United States. They have revolutionized the way they approach the designs and the way they review the data. And they have breakthrough designation status they’ll give to compounds that are really looking like they have strong efficacy. And so, the approval process through the agency has improved remarkably. And they’re open to adaptive designs. And they are open to interim analysis. And they are open to all sorts of things.

So, I really wanted to give credit to our agency who has said, “Where there’s a need for breakthrough medications, we’ll try to find the path.” And so, I do believe there’s a real positive side to this. The challenge is the market is saturated. We have now more than 25 PD1s in development. And to put the 25th one in there, they are so far behind in development. I wonder what that does. It clogs up the system. So, when you look at how can we influence sites, at the top sites we only get one or two patients.

And we compete with 50, 60, 70, 80 other sponsors. And so, it becomes so saturated that, that site has to learn to do systems and process with 70 companies. And what they are doing is almost hedging. They are not focusing on certain things. So, in those cancer centers, they offer treatment for all lines of therapy and all types of cancer, the specialized and nonspecialized. And we are moving out of that sort of geography and moving it community-based oncology practices where it’s less saturated, and we can actually have more traction there and be able to engage more with the clinical trial enterprise for the good of the patients.

Andrew Schorr:

Ken, you write books about all kinds of issues around this. So, if we are getting—particularly in oncology to have trials offered at the community practice where those doctors work night and day—the nurses. They are really stretched. More and more cancers, genomic subtypes, most sophisticated testing. How—what would you say the patient can do. T.J. talked about it a little bit. What would you recommend to patients so that at that community oncology practice the patient and the family can kind of discover what may be available for them as Merck and other companies try to get these trials distributed?

Ken Getz:
Right, well you—talk about the whole enchilada, Andrew. You’re really touching on it. It’s also very exciting times for patients, not just cancer patients, but patients that are dealing with any chronic and severe illness today. And it’s really all about more of a partnership with the clinical care environment and clinical research. And of course, at the heart of it is the patients and their family being as informed as possible, sharing their electronic health and medical information so that they can be connected to trials that might be appropriate for them.

But it’s moving—as Andy said, away from the classic places where trials used to be conducted. And in many cases, they were at these dedicated centers that only conducted clinical trials. It’s a very competitive environment now for patients. So, many sponsor companies like Merck and others are looking at clinical care settings and moving into communities or, in some cases, large health systems where you can have clinical research professionals who will supplement and provide support to the healthcare providers, so they’re not stretched too thin.

But so that they have the clinical research capability onsite at the point of care. For patients it’s a great opportunity because now they have the opportunity to get their own healthcare or treating physician and treating nurse involved in a clinical trial as part of their overall care. And we expect to see more of that over time. We expect to see other virtual trials or opportunities for patients to participate in the comfort of their own home tied in with their clinical care setting.

And all of this is relatively new to the whole world of clinical trials and the investigation of experimental medications.

Andrew Schorr:

You touched on something I just want to follow up on. I’ve heard of this term site-less trials where you said you participate in your home. So, T.J. had to go from Ft. Lauderdale to Tampa. I had to go from Seattle to Houston. There are not—this is a big deal, especially if you have little kids as I did, he has. So—and away from work and whatever your situation is. So, is technology going to come in play so Andy can get the data he needs for the FDA, but that we can have technology help accrue that data in a more efficient way.

Ken Getz:

And I’ll say absolutely. And my colleagues here today I’m sure can comment on this as well. But absolutely. We are seeing wearable technologies and mobile applications that now have the ability measure vital signs and other important baseline information in a validated manner. There are ways that you can access a specific facility for a highly specialized test, specialized imaging for example where the technician can evaluate it remotely. Blood can be drawn at remote locations as well.

So, there are lots of places where we have sort of this more flexible environment that can cater more to the patients and less about a specific physical facility where you have to go to participate in a trial.

Andrew Schorr:
T.J., I want to talk to you about diversity. So, you and I are kind of middle-class white guys. But we want to know how new medicines work for a variety of populations, ethnically, economic groups, et cetera. And Andy needs that data. And he goes to the FDA, and the FDA says, “Well, do you have Hispanic people? Do you have Asian people? Do you have African American people?” or whatever the country is because he works globally. And they say, “We want to understand are there differences?”

How are we doing with that. How can we make a difference there so that we really know what medicines make a difference for broader and also distinct populations?

T.J. Sharpe:
I’m sure Ken can back up some of these things with more hard data than I can. I know that different populations have different levels of trust with the medical system. One thing that you and I both experienced was a lack of options—a lack of good options. And when you get into dire straits, you tend to be a little more trustful of anything that comes along. But we have serious or chronic conditions that have proven treatments that might not be the most effective for certain populations.

And we’re not able to broad the scope to these minority populations or populations that don’t have access to NCI designated cancer centers or top-notch medical facilities. They are not able to get either in a trial that is looking for a drug that would help them or even get access to medicines that have been recently approved simply because their healthcare situation doesn’t allow it. Whether that’s a lack of insurance, a lack of healthcare literacy or simply a mistrust of—there’s a lot of generational mistrust I think in some communities of the clinical trial system.

So, as an advocate, I certainly push caretakers especially—and children caregivers for older populations who are maybe first or second-generation Americans to help facilitate a conversation between the medical professional who’s trusted and a patient that might not be able to get or rely on the information they’re given. Because it really will speak to populations that don’t get the opportunities that you and I have gotten simply because they are either not aware, or there is a barrier there to get to that medical professional.

Ken Getz:

I appreciate, T.J., you mentioned CISCRP. That’s one of the things that we’ve focused on for 18 years is bringing clinical research education into major metropolitan areas around the U.S. and parts of northern and western Europe where we plan for several months, and then we put on what we call an Aware for All events. And we really work very hard to encourage participation by—or from patients based within minority or underserved communities.

And I’m happy to say that we’ve had a lot of success with that. These are really difficult communities to reach through a lot of the traditional approaches. We have to rely on community centers and clergy and other approaches to really help these communities, for a lot of the reasons T.J. mentioned, trust the educational information, and come out to learn more. And I’m happy to say we’re seeing more and more people of diverse backgrounds that are curious and interested in learning more about clinical research, especially knowing that representative populations provide more information that can inform treatment for different types of patient sub-populations.

Andrew Schorr:
I want to go to Andy in a second. Andy, just one second. I wanted to mention and call out—and Andy’s company has been a leader in this. He was talking about PD1 and all of that. But drugs that have been breakthrough in immunotherapy for people like T.J. where—and it’s being explored in broader cancers where otherwise life was going to be short. And how to activate the immune system and really fight the cancer in people living long term. So, the people in those trials—and certainly there were people in the melanoma trials like yourself T.J.

Lung cancer trials and increasingly now others who did get tomorrow’s medicine today. Andy talked about accelerated approval which is great. So, that’s the impetus for the patient and the family. Is there the chance to get tomorrow’s medicine today? Now the obstacles may be distrust. You talked about that, Ken. And also, is maybe accessibility. Is it as a clinic near you? And Andy you talked about pushing that out. And then sometimes it’s related to cost.

Now is there anything that sponsors can do, Andy, related to the costs that people may have in being in certain trials? Where do we stand with that?

Andy Lee:

Yeah, so I’ll just touch on the distribution first and then get into the costs because they are linked. When we prosecute global trials—we’ve had a very U.S.-centric discussion so far. But cancers present differently in different geographic regions of the world. And so, when we want speed out of our trials. You want me to shorten that timeline and get drugs to market quickly. I do it internationally and in some cancers like esophageal cancer or some of the gastrointestinal cancers, Asia has a much higher prevalence of these cancers.

And we do a greater proportion of work there. We always include multi-country studies. And U.S. may have a greater proportion in other areas. So, we balance that out to optimize speed. Of course, with clinical trials the cost structure around the globe is very different. But let’s talk about U.S. We have spoken about a saturated core of clinical trial sites that we all go to. And I speak generally now for all sponsors. And we are all looking to optimize and get great efficiency.

At the same time, we realize we have many underrepresented geographies and ethnic groups—and not just ethnic groups, but under resourced populations. And so, what we’ve been thinking about is how can we support people, and support people at all levels. And so, we start off with thinking about the cost structure, and we obviously pay clinical sites for what they do. But we will support all sorts of things. We’ve been negotiating with Uber and Lyft, so we can build that into automated transport for patients.

Again, the IRB has to approve that. We are looking at ways to augment that they are not out-of-pocket for things. And we’ve been talking a lot with a group called Lazarex Foundation who has really expanded into under resourced communities and found ways to ensure that they have daycare and different access for those patients. We have worked extensively now to look at outreach programs into communities that typically wouldn’t be in trials. We are focusing in two areas right now as we speak.

One is next generation of HIV medicines, and the other one is in prostate cancer. And we’ve got a large program rolling out in prostate cancer. So, what we are doing is going into sites and we have put together training videos and training materials. And we are looking at cultural competency. So, it starts at the site. Are they culturally competent to engage a different community? And we’ve spoken about working with the community churches, community education systems.

And so that starts with cultural competency. I have a woman, Madelyn Goday, who works on this day and night in my organization. And she’s very strong at this. It’s early days, but if we can show that it works in one or two therapeutic areas and cancer types, we’d expand it further and further. But we can’t just have a shotgun approach and just go and do 100 sites and hope it works. Hope isn’t a good strategy. We are working systematically to engage different people. And as appropriate and approved by ethics committees, we will support all of these communities and help build infrastructure and capacity.

Those are important things for us. But as I said, where appropriate and where it’s sustainable. We can’t just throw money at something in the hopes something sticks. We have to have something sustainable and it goes to what Ken says, and that’s education and providing resources and materials. And we’ve used quite a lot of Ken’s materials in multiple clinical trials. Thank you for that, Ken. It’s been really helpful for us.

Andrew Schorr:

Great. I wanted to note for your audience. If you have a question, send it to questions@patientpower.info. We have expert panelists here. And this is really—we are all in this together. I think you hear the dedication from Andy at Merck and T.J. as a patient advocate and Ken as a professor and founder of organizations devoted to this. We want obviously accelerate medicines, but have the accurate data of how it affects different people, who is it right for so that the regulators—and thank you for what you said about the FDA here in the U.S., has the information to make a decision on should this medicine be available for people with that diagnosis.

Okay, so what about staying in the trial. So, T.J., how long—let’s take with the Keytruda trial or one of them. How long were you in to for?

T.J. Sharpe:

Nearly four years. Three-and-a-half years.

Andrew Schorr:

Were there ever times when you said, “I’m done. I want to bail out.” You know.

T.J. Sharpe:

I’ll be very careful how I answer this question for Andy’s sake.

Andy Lee:

It’s okay, T.J., we’re friends.

T.J. Sharpe:

No, probably the biggest crossroads I ever came to was when one of my tumors started growing about a year into it. And we weren’t sure if the medicine stopped working or not. We didn’t know what to do. And as it turned out, it was still working. And I think was just one spot that wasn’t responding. But everything else had responded great. However, at the point, as a patient, you’re thinking about yourself first and your family first and the trial second. It’s easy to stay compliant on a trial when things are going well.

But when you’re ahead of the medicine in some ways, and I think patients with chronic illnesses or in some cases rare diseases, are almost more knowledgeable than some of their doctors or the trial protocols about when they’re stopping. They don’t have the luxury of finishing out a protocol and seeing where their disease journey takes them. And the best example I can give of this is a very passionate advocate by the name of Jack Wheelen who we unfortunately lost a couple of years ago, but whose influence has kind of dominated the patient advocacy world for the last decade or so.

And Jack was able to monitor his health almost better than a doctor. And he knew when his trials weren’t working. When we get to that point in a clinical trial setting where we know the medicine is not being effective or where a patient would be better served to move on to another treatment. That’s when we are going to take the next step in clinical research, because now we’re aligning the trial design and the trial goals with a patient and a patient’s family’s treatment goals. And as those two points merge, that’s where clinical research becomes that much more effective as a care option.

Andrew Schorr:

That was well said. And I think with all those trials, you’re right, the team—that care team, what’s right for you at that time. Obviously to get the data, but also not at all costs. In other words, if the data is showing something is no longer effective for you, is there another treatment or a trial? I’ll just share my story for a second. So, I was in a phase two trial of combination therapies—which are increasingly common certainly in oncology. And after three months—halfway in the trial, my blood was kind of cleaned up.

And I had nausea and some other side effects. And I said to the trial coordinator, “You know, I think I’d like to stop.” And she said, “You know, our belief is that you still have microscopic illness in your bone marrow—in this case with the blood cancer, and the additional three months in this protocol will make a long-term difference for you. That’s what we believe.” They didn’t have the answer, but that’s what they believed. You know what? I stuck it out. She was right. I had 17-year remission.

If I’d stopped after three months, would I have? So, it’s a dialogue with the care team Andy, right? It’s this ongoing discussion not just entering the trial, but remaining in the trial, correct?

Andy Lee:

Yes. Absolutely. And I just wanted to impress a really important thing. People talk about people dropping out of trials. In cancer trials we see extremely low drop out. I mean these are potentially lifesaving medicines for all of the companies. But what we do want to make sure about is that when there is progression of disease, and it’s shown that the drug—whichever it is, the control arm or the active arm or the new agent, where there is progression of disease that they get the best available therapy.

And so that often contaminates trials because we have the crossover effect that now they are getting maybe the experimental agent in the standard of care type of thing. But most important thing for us is to track the survival of the patient, regardless of whether they go on another therapy. And we have put a tremendous amount of effort into looking at the informed consent and making sure we work with IRB to track patients long term survival.

Because as you’ve said, you may have a short-term issue that shows that the drug may not be working short term, but long term it may have prolonged and profound effects. Positive or negative, we don’t know that. And so, what we like to do is get long term survival. And we ask patients to consider when they sign the consent for whatever trial and whichever sponsor is sponsoring this, is to consider that knowing their status throughout their treatment—whether it’s on a sponsor’s drug or another sponsor’s drug or x therapy. It is really important — and I ask people to think about that.

Because that really helps us get as much data out of the individual treatment as possible. And that may prevent nonrequired trials in the future or it may say, “Wow, that really informed.” And we’d like to inform all cancer patients. If data we generate can inform other therapies, we certainly want to do that. We do not want to do wasteful clinical trials. So, tracking patients long term or patients—the message to patients is being cognizant of letting the sponsor—and the sponsor could be an institution. Letting them know your status is really important. All they want to know is are you dead or alive.

Andrew Schorr:

In the end, just one thing is, are we partners. In the end, our viewers here, are we your partner? And can we feel that not just for their doctor but you guys behind the scenes with the labs and everything, that in the end we are partners. And unless we see it that way, we won’t get anywhere.

Andy Lee:

Absolutely. I’m glad you used the term partners. Because when we’ve done a prep for this people have said, “Are they investors in the thing?” So, yes, patients invest their time and everything, but they are partners in research. They are contributing so much. They are contributing—they are going into the absolute unknown. And there is an immense trust level that is there. And we owe that back as research professionals is to treat people with respect, dignity and as partners, to make information available, to publish our data to get it out there as quickly as possible. And to make sure we get that back into the participant’s sort of hands.

Andrew Schorr:

So, Ken, how are we doing on that because you go back over the years and people say, “I don’t want to be in a trial because I’ll be a guinea pig,” and respect was not seen as part of it.

Ken Getz:
Well, that’s also a bit of a myth, right? You had a few that claimed that they felt the process made them feel like a guinea pig. The vast majority of people, over 90% of people who participate in a trial, would do it again. So, once they get past that unfamiliar area where they’ve perhaps only heard a few case examples or a few very vocal people who had bad experiences. Once they’ve done it themselves or they’ve been able to work with a group of advocates that really help them think about this process, and they become more educated, generally they’re very impressed with the level of professionalism, the compassion that exists at all levels.

I work with so many professionals—science professionals and pharmaceutical companies and at the research centers, and they all share that kind of commitment that Andy just mentioned. There’s a real desire to partner with the patient to really inform them. I would say one place where we need to see much, much more however is in the return of clinical trial results in a plain language to people who’ve been in trials. That’s a place where as an enterprise—government, research sponsors as well as industry have not really made this a standard practice at this point. And that’s one thing that we’re really working on actively.

Andrew Schorr:

Right. Great. So, T.J., you and I are investors—and Ken used that term and Andy used it, and I’ve always believed it. We are investors of our tissue, our body, our future to help other people and hopefully help ourselves. And certainly, for profit companies that may greatly benefit if they have a blockbuster therapy. But we need to be kept informed in the long term, right T.J.? We want to know what a difference our participation made.

T.J. Sharpe:

Certainly. And I think to echo what both Andy and Ken said is that patients do become partners. Patients who are involved in clinical research, a significant chunk become altruistically invested. I’ve heard more than once, “Even if this doesn’t help me, I’m glad I participated because it might help somebody else.” I know I’ve felt like that, and I’d venture that you’ve had some of that too, Andrew on your journey. So, it’s only—it’s at the very minimal fair, and it’s certainly very justified to expect as a co-participant in this.

And as kind of a co-creator of science with sites and sponsors that we understand what has come of our sacrifice and our time dedication to helping science out. We shouldn’t have to find it out through press releases from ASCO or hope that we hear about it on the nightly news. We deserve to hear what has happened. Not just because it can affect us as people and as patients, but that we put a lot into this too. And then we did our part to further medical research and we want to be part of the—whatever the end of the trial ends up being. We want to be aware of that. Not just for personal knowledge, but to know that it’s going to help this many other people.

Andrew Schorr:

Right, to be honored. So, Andy, at Merck you’ve established some internet platforms in particular related to keeping people informed, right?

Andy Lee:

Well, we’ve got an internet platform that people can log onto. I’m happy to share that with you; in which they can get access to a list of our trials. So, I didn’t prepare this but especially, but I did make a handmade note. And if anyone wants, it’s a very simple log on. Andrew Schorr:
You’re a great artist.

Andy Lee:

And it’s a simple one. What that will get you access to is two main important things. One is it gives access to information about clinical trials. We have a tab on there that tells everyone about the phases of clinical trials and what to expect in a trial. So, it’s an educational part. Then we have a lot of information about the Keytruda clinical trials were, are running, and they’re called keynote trials. And there you can look at the different indications. And you can look up and it has a telephone number you can call.

Now I must stress is that we run over 1,000 clinical trials in oncology. But many of them are not sponsored by us, they are investigator sponsored trials. So, you can go to clinics, and they run their own clinical trials that are not sponsor-related. And the NCI runs their clinical trials. So, there are a lot of different sources. And many companies will have clinical trials. We also have the website clinicaltrials.gov. I’ve had to use that in the last two days for a colleague.

And you can navigate that and look for different types of trials. And you can look at different products and everything. It’s not perfect. But at least it’s a place to go to. And I don’t want to sound as if I’m one sponsor centric. Many other companies have access to websites, and they really want to try and enhance and direct people to the clinical trials sites at which they are working.

Andrew Schorr:

Right, absolutely. And then you were working at the industry level with a group called TransCelerate, and I know T.J. is involved too, to try and establish common procedures as you establish trial sites, as you have communication, as you have training, right? So, that hopefully all boats will rise, right?

Andy Lee:

That’s correct. TransCelerate is a group that formed about eight or nine years ago. There were 10 initial member companies. I was a founder member of that. And we got together to say, “We have to improve operational efficiency.” So, we do not collaborate on molecular structures and those types—that’s competitive. We collaborate on what we call precompetitive, procompetitive aspects which says, “If we all work together to improve something, we’ll all get the benefit of this.” And we share it publicly.

There’s a website, you can look at it. But we’ve looked at standardizing protocols. We have a common protocol template. We’ve adopted that at our companies, so have other sponsors. The protocol can be developed in a standardized way. We’ve looked at standardizing ways where we can improve monitoring. We’re looking now at ways that we can work with investigative sites through i-platforms, shared investigative platforms. So, a clinical trial site has to provide the information for us as a sponsor and use the exact same standardized questionnaire and information for any other sponsor through a standard portal.

So, we are trying to reduce the burden on clinical trial sites. And we’ve plugged away for many years, and we are seeing greater traction there. We are seeing more efficiency, more standardization. We are seeing greater quality, less rework. And so, while it’s hard to quantify this, what we believe is that the sites are freed up of some of the more burdensome things, and they can direct their attention towards patients, patient safety, and access to clinical trials. So, the work may not be directly related to access for a cancer patient into a cancer trial, but there’s a lot of tangential spin-off of making a site more efficient so they can put their resources and energy in the right place.

Andrew Schorr:

Well, thank you for that effort and your leadership. So, Ken, you’ve been around this a long time. And you’ve deal with all the companies and the government and the various agencies. And as you know, in some quarters there’s a distrust for pharma. We mentioned cancer that you get the price tag of a drug, and it’s very expensive. And some people are struggling to pay for it. And there’s just frustration about it. And often in the news media they are the bad guys who are called out for unethical procedure or something that went awry.

So, how are we doing there in overcoming that because we talk to Andy, he seems very ethical, dedicated guy representing a company that’s been around I think well over 100 years. So, how are we doing to move clinical trials on in this area when people aren’t sure what to make of pharma.

Ken Getz:

Yeah. It’s a huge issue, Andrew. And I think part of the challenge is that all it takes is one questionable behavior, and it makes it difficult for the reputation of the entire industry. Right now, we are dealing with major pharma companies that are actually being fined for having contributed—a judgement, having contributed to the opioid crisis. And when you start looking at some companies aggressive marketing tactics, right? It really sort of sheds a darker light on a lot of the great work that companies do.

What we look at, at the Tufts Center for the Study of Drug Development at the School of Medicine. We look at the overall output, the level of innovation that’s coming from the industry today. And we look at the number of complaints that have been filed with the FDA and other regulatory agencies around the world. And what we see is tremendous growth in the innovation and the quality of the innovation—drugs like Keytruda and other cancer immunotherapies. What an exciting area.

We see that the vast majority of companies really support and live by highly ethical, highly professional, highly compassionate approaches because they all know that it takes just one questionable issue that can really tarnish the reputation of every company operating in the industry. So—again, Andy also mentioned just how regulated we are as an industry, the fact that we have ethical review committees and data safety monitoring boards and so many other external agencies that help to oversee the work that’s done here.

So, I would say for patients who are thinking about clinical trials, it’s good to know the history. It’s good to know what you need to do to protect yourself. But the vast majority find that the people they deal with are ethical, they are professional, they are compassionate. And, as I mentioned, over 90% of people who get involved in trials say that they would do it again.

Andrew Schorr:

Thank you. That was a wonderful response. Andy, you mentioned earlier about starting research with the sickest people basically, where there are no options. But one of the questions that came in is, “Are trials only for the sickest people or are there of all those trials you talked about opportunities for people who maybe are newly diagnosed or could be their fairly initial therapy?

Andy Lee:

Yeah, great question. And thank you to the person who asked that. And the answer is that we start in people—because we don’t know if our experimental agent will work. And everyone assumes that new medicines are all going to succeed. And we work in research and researcher because of that many things fail very early on. They fail in phase one before anyone hears of it. It’s normally a code number at that point. And we may just not make the drug soluble enough, or it may not be distributed enough.

So, we may have a thing that works in a test tube or a petri dish. But to get that into humans and make sure that it’s safe at the dosage we use often fails. We just don’t progress far enough. So, what we want to make sure of is that firstly the drugs are safe. And there’s a trade-off between safety and efficacy. We’re constantly trading off. And so, what we do is we look at that and say when someone has no option and we want to get an option going, that’s where we start.

We’ve actually moved down the disease scale, and we’ve come into adjuvant treatment or secondary prevention. And we’ve gone into newer adjuvant is when you have a small tumor is we pre-treat to manage that tumor before surgery is done. And post-surgery we hope that there’s limited treatment or no treatment. And we actually have removed the cancer, and there would be no evidence of disease. But. of course, using the word cured is something we try not to do, because we prefer to use no evidence of disease.

But absolutely. And the next strategy is prevention of cancer. Our company does a lot of vaccinations in women’s health. We have a product that protects against human papilloma virus which is a precursor for cervical cancer. So, people who are vaccinated with this particular product—and I’m deliberately not using brand names for obvious reasons. But when you vaccinate for HPV, you essentially are preventing the likelihood of a cervical cancer. And there are now prospects in many disease areas where either vaccination or early treatment gives you a tremendous positive prognosis of not getting the disease later on in life.

The answer to your question is yes, we are absolutely looking at ways to prevent getting to a very advanced stage which is very costly to manage and very emotional and stressful and difficult.

Andrew Schorr:

I want to thank you. I just want to get a final comment on what you would say to patients or family member. And I want to start with you, Ken. What do you want patients right now to know so that—what tips would you give them so that they’d consider being part of clinical research or stay in clinical research and the benefit it could be for them.

Ken Getz:

I will say really two things. The first is there’s just a tremendous amount of information out there, and we recommend education before participation. So, do your homework and engage family and friends and people you meet and trust to help you make the decision. And the second point comes off of that. And that is this is not a decision you make alone. Really bring in your treating physician, your nurse. Bring in your support network. And chances are you will learn a lot, and you might even find a trial that is right for you.

Andrew Schorr:

Right. And Andy, what about you? A final point—what would you say to a friend or family member or colleague related to considering trials today.

Andy Lee:

We get this question every single day. And we get it from patients in need. And my answer is we are all patients. We are all going to face this as professionals in our job or professionals outside. And so, I say community of practice. And disease hits all of levels of society in all education professions, et cetera. And so, my thing is to encourage people to do what Ken has said. Work as a team. Get multiple inputs.

And I am sponsor agnostic. Get the best therapy that is available. And that may be the best care option—as I said, the ecosystem in which you get the care is really important as well as the medicines that you get. So, have the discussion. Trust the medical professionals, they are very skilled out there. They are extremely well educated. And I just urge people, “Don’t think on two clicks on Google you are going to solve what your treatment option is.” Really discuss it with people because not all the options are public, and there is not enough information available about how to manage the whole disease through the entire enterprise. Trust the professionals.

Andrew Schorr:

Well said. And T.J., you and I are alive today because of trials. What do you want—what’s the thing you want to leave our viewers with?

T.J. Sharpe:

That they don’t have to be involved in clinical research. I think that’s an important distinction to make. And it’s going to pull together what Andy and Ken said that clinical research should not be considered a hail mary or last gasp option. If you are a patient—and we are all going to be patients as Andy mentioned. You want the best care for you. You want to be able to weigh all of your options. And if you are not considering clinical research, if you don’t know about it or aren’t able to get the information you need about it, then you are not going to be able to make the best healthcare decision long term for your health.

So, take that information that you can get. Find the trusted sources. Be able to reach out to advocates or colleagues or someone that you know that would have the disease or can connect you with good information. And be your own advocate—a little cliché, but really own that healthcare information. And once you are able to collect all of the different treatment options, then you consult with your professional medical team as to what the plan forward—the best plan forward for your individual situation would be.

Andrew Schorr:

Right. T.J., my friend, thank you. It’s a delight to see you again. Andy, with Merck, thank you so much for being with us and bringing your years of expertise. And, Ken, being at an independent non-profit center and also at Tufts University there, thank you for all the work you do. I want to thank the Patient Empowerment Network for pulling this all together. And the sponsors who supported us in this effort, AbbVie Inc., Celgene Corporation. Daiichi Sankyo and Novartis.

All these companies and I’m sure many more, working so that research can move forward. We can be true partners in it. And hopefully get tomorrow’s medicine today to make a difference for the community and live a long life, and hopefully a cure, right? I’m Andrew Schorr in California. Remember, knowledge can be the best medicine of all.


Please remember the opinions expressed on Patient Empowerment Network (PEN) are not necessarily the views of our sponsors, contributors, partners or PEN. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.