Tag Archive for: ADC

Lung Cancer Treatment Plan Advice | Where Do Clinical Trials Fit In?

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Lung Cancer Treatment Plan Advice | Where Do Clinical Trials Fit In? from Patient Empowerment Network on Vimeo.

What questions should patients ask about a lung cancer treatment plan? Lung cancer expert Dr. Thomas Marron shares key considerations when choosing therapy and discusses where clinical trials fit into planning.

Dr. Thomas Marron is Director of the Early Phase Trials Unit at the Tisch Cancer Institute at Mount Sinai Hospital. Dr. Marron is also Professor of Medicine and Professor of Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai. Learn more about Dr. Marron.

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 What Are the Advantages of Seeking Care With a Lung Cancer Specialist?

What Are the Advantages of Seeking Care With a Lung Cancer Specialist?

Transcript:

Katherine Banwell:

What questions should patients be asking about their proposed treatment plan? 

Dr. Thomas Marron:

I think that in lung cancer, most patients are going  to get the same therapeutic approach offered to them wherever they go.  

It’s not like certain types of cancer where there’s 10 different ways to treat it. But there are some nuances and depending on the location in which you’re getting treated, whether it be in an academic hospital or a community setting, you may have different chemotherapies offered, immunotherapies offered. You may have different combinations offered. And so, I think it’s important to always ask your provider what other options are there, and why are they recommending one option over another. But I think it’s also really important that patients get second opinions.   

A lot of my patients, even my in-laws are always very skittish about getting a second opinion because they don’t want to insult their doctor, who they feel very close to. And I would say, it couldn’t be further from the truth. Any good doctor is 100 percent okay with a patient going and getting a second, third, fourth opinion because to us, the most important thing is that you have confidence in the decisions that we’re making about your treatment.

I always tell patients, I’m basically a waiter here offering you a menu of options and giving you my recommendation. But it is up to the patient in the end what treatment they receive and how long they receive it for.  

And if they decide ever to discontinue it. And I think that the more information, the more smart people looking at you, the better.  

Katherine Banwell:

Where do clinical trials fit into a non-small cell lung cancer treatment plan? 

Dr. Thomas Marron:

So, that’s a phenomenal question and one that I hope that everyone asks their providers when they see them because the reality is that while we are curing some patients, the vast majority of patients are not cured. And I think that all patients should at least consider a clinical trial, whether it be a first line clinical trial. So, the first medicine that you receive for your cancer, or at the time of progression.  

I think particularly, once patients progress on the first line therapy, those patients we really don’t have a cure for, even if we have some palliative chemotherapies or eventually these antibody drug conjugates to treat them.  

And so, I think everybody who is progressing on first line therapy should always consider a clinical trial. And I think it’s extremely important that patients realize the need to ask their providers about clinical trials, but also be an advocate for themselves and go out and get second opinions, get third opinions and see what trials are available in the community and even in other cities.

Because often times in New York City, I’ll have completely different clinical trials than my colleagues at the other five institutions in the city. And it’s really important that patients advocate for themselves, and they identify everything that’s available.   

Antibody Drug Conjugates for Lung Cancer | Advances in Research

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Antibody Drug Conjugates for Lung Cancer | Advances in Research from Patient Empowerment Network on Vimeo.

What are antibody drug conjugates, and how are these new agents changing lung cancer care? Lung cancer expert Dr. Thomas Marron defines antibody drug conjugates and explains how they work to treat lung cancer.

Dr. Thomas Marron is Director of the Early Phase Trials Unit at the Tisch Cancer Institute at Mount Sinai Hospital. Dr. Marron is also Professor of Medicine and Professor of Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai. Learn more about Dr. Marron.

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Transcript:

Katherine Banwell:

What are antibody drug conjugates, and how do they treat lung cancer?   

Dr. Thomas Marron:

So, antibodies are proteins that have been manufactured. They’re a synthetic version of something that happens in our own body And they’re very specific for a very unique protein. And so, there are certain cancer proteins, there’s proteins on the surface of cancer that really aren’t expressed anywhere else in your body. And so, what we can do is we can develop these antibodies that basically are a heat-seeking missile. So, you inject them like chemotherapy, through an IV. But they’re a heat-sinking missile, and they go throughout your body, and they stick themselves to the cancer.  

And hopefully, they don’t stick anywhere else. And basically, antibody drug conjugate means the drug is conjugated to the antibody, meaning you basically have glued chemotherapy onto that antibody.  

And so, what it allows us to do is, instead of giving chemotherapy through the IV like we normally would, where that chemotherapy goes everywhere in your body, and that’s the main reason that you have toxicity.  

It doesn’t just go to the cancer, it also goes to your bone marrow, to your hair, to your intestines, has side effects. Antibody drug conjugates, the goal of them is to really deliver the chemotherapy directly to the tumor and spare the rest of your body, the toxicity from the chemotherapy that’s glued onto the antibody.

It’s important to note that they still do have side effects. So, some of that chemotherapy, for lack of a better term falls off the antibody or it might leak out of the tumor after it kills the tumor cells. And so, there is still the potential for toxicity, very similar to the toxicities that we see with chemotherapy.   

But so far, the data is very encouraging, both in lung cancer and other cancer types that antibody drug conjugates might be a superior formulation of chemotherapy, so better able to treat lung cancer. And we have a few drugs that’re actually probably going to be FDA-approved in the second line setting for non-small cell lung cancer. So, that’s for patients who have received standard first-line therapy and unfortunately, their cancer has progressed.   

And we actually already have one drug that was, it’s called Enhertu that was developed for breast cancer. And that’s now FDA-approved for lung cancer, for a rare subset of lung cancer patients who have an exon-20 HER2 mutation.  

And the patients I’ve treated with that drug do extremely well, and so I think it’s a very encouraging sign of what’s to come using more and more of these targeted chemotherapy regimens.  

Katherine Banwell:

Yeah. Well, that leads me to the next question, is there a patient type that ADCs are right for? 

Dr. Thomas Marron:

So, maybe is the question, answer. So, I don’t know because we don’t have good biomarkers right now to identify the patients that’re going to respond best to the drugs that’re in development, at least those ones that’re furthest along in development.  

And we’re always searching for biomarkers, which basically just means a test that we do on the patient’s biopsy or in their blood to tell us who’s going to respond to a therapy and who’s not. Unfortunately, right now we don’t have a good biomarker for these drugs.  

Hopefully as we do larger trials and we study biopsies and blood from the patients on those trials, we can identify the subset of patients that will do best with the therapy. Because we always want to make sure we’re getting patients the best therapy for them and we’re avoiding giving these therapies, because there are some toxicities to patients that aren’t going to respond to the therapy. So, it’s definitely a work in progress. 

Advances in Targeted Lung Cancer Treatments | What You Should Know

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Advances in Targeted Lung Cancer Treatments | What You Should Know from Patient Empowerment Network on Vimeo.

Dr. Thomas Marron discusses how these therapies work to treat lung cancer, how the presence of certain mutations can impact care and treatment choices, and the research being done on new therapies to target specific lung cancer biomarkers.

Dr. Thomas Marron is Director of the Early Phase Trials Unit at the Tisch Cancer Institute at Mount Sinai Hospital. Dr. Marron is also Professor of Medicine and Professor of Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai. Learn more about Dr. Marron.

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Transcript:

Katherine Banwell:

Welcome, Dr. Marron. Would you introduce yourself, please? 

Dr. Thomas Marron:

Sure, I’m Tom Marron. I’m the Director of the Early Phase Trials Unit at the Tisch Cancer Institute at Mount Sinai Hospital. I’m a Professor of Medicine and also a Professor of Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai. And I’m trained as both an oncologist and an immunologist.  

Katherine Banwell:

Excellent. Thanks for joining us today.  

Dr. Thomas Marron:

Thank you for having me.   

Katherine Banwell:

We know that the presence of certain mutations can affect lung cancer treatment options. Can you share the latest updates in targeted therapies?  

Dr. Thomas Marron:

Sure, so there’s been a lot of developments in targeted therapies as of late.  

Mutations in a patient’s cancer can represent a potential therapeutic target, and we have increasing numbers, every year we have new FDA approvals for typically pills that target very specific mutations and are able to either control cancer or even kill cancer. Additionally, we use DNA sequencing of tumors to identify mutations that could be predictive of a response to certain therapies. So, even though we don’t have a specific drug to target that mutation in their DNA, that change in their DNA that’s making the cancer grow, we do know that patients with certain DNA mutations do better on certain therapies than other therapies.  

And so, we can use mutations specifically to help guide therapy, even if we don’t have a targeted therapy for something like EGFR mutation or a KRAS mutation. And additionally, one of the things that we do as we’re treating patients is, often times we will give a patient with lung cancer a therapy and then their cancer may respond for weeks, months, even years.  

But then it might recur, or it might just start growing if it never went away entirely. And at that time, we’re oftentimes repeating the genetic sequencing, whether doing a biopsy or sometimes we can do what we call a liquid biopsy, which is just taking some blood and looking for some of the DNA from the cancer floating around in the blood.  

And the reason we do that is that if you see a change in the mutations, it might represent either a change in the type of cancer or it might represent what we call an escape mutation, or an escape mechanism where the cancer that had been responding to therapy X is now not responding because it changed its DNA to overcome the therapy you were given. And that might suggest that we try a specific new therapy, or that we just change our approach entirely.  

Katherine Banwell:

You’ve answered my next question to some degree, but I’m going to ask it anyway. How do these therapies work to treat lung cancer? 

Dr. Thomas Marron:

So, cancer is caused by changes in your DNA. So, your DNA is your instruction booklet on how cells should grow and when they should grow. And every cell in your body theoretically has the same DNA, except for, because of a variety of things like smoking or exposure to radon or just living in a large city full of pollution. As we get older, we basically accrue more and more mutations and changes in our DNA, our instruction booklet. And while most of these changes really don’t have any sequela, and they’re not going to affect the ability for the cancer, or for normal cells to grow.  

Sometimes you’ll get a mutation in a very specific gene that’s important for telling cells when to divide and when to grow and when not to grow. And you can think of it as a light switch where the light switch gets stuck in the on position and constantly, cells are growing and growing and growing and that’s when you have cancer. So, when you have these mutations, one of the approaches that we’ve been working on for the last few decades, in particular in the last few years.  

We have lots of these new drugs that target these mutations, and they basically turn that on signal off. So, they disrupt, it’s like turning the light switch off. You’re disrupting the constant grow, grow, grow signal and keeping the cancer from growing. Typically, we think of these targeted therapies that do this, not as cures for cancer, at least when patients have metastatic disease, but they’re very good at controlling cancer. And some of these therapies can work for years, even a decade and control the cancer. But often times, unfortunately cancer always finds a way to outsmart us, even when we’re outsmarting it.  

Katherine Banwell:

Right. Are there new mutations being discovered that can impact the future of small cell lung cancer care? 

Dr. Thomas Marron:

Well, I’m not sure I would say that there’s a lot of new mutations that’ve been discovered, per se. Every time that you come in and get a diagnosis of lung cancer, we typically will take the tissue and like I said, sometimes we’ll take some blood and do a liquid biopsy and look for a slew of different known mutations.   

And typically, we’ll look for anywhere from three to 500 known mutations in the cancer, even though we only have drugs to treat about 10 of those three to 500. The nice thing though is that as we learn more and more and more about these mutations and we study them, we are developing more and more drugs to address specific mutations. So, five years ago we really only had three different mutations that we could target.  

Now, we have around 10 because we have all these new drugs that target very specific mutations whether they be in genes like MET or RET or KRAS or BRAS.  

So, I think that while we aren’t necessarily discovering that many new genes, we’ve been looking at the genetic sequence of cancer and also, just the human genome for 20 to 30 years at this point, we’re discovering lots of new drugs that can target those specific mutations that we know patients have, but that most of the mutations we identify are not necessarily druggable targets.  

Advances in Small Cell Lung Cancer Research | Hope for the Future

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Advances in Small Cell Lung Cancer Research | Hope for the Future from Patient Empowerment Network on Vimeo.

What new treatments are being studied for small cell lung cancer (SCLC)? Dr. Triparna Sen, a leading researcher in the field, shares promising updates, including advances being made with LSD1 inhibitors, DDR (DNA Damage Response) inhibitors, and DLL-3 targeted therapies.

Dr. Triparna Sen is an associate professor in the department of oncological sciences and co-director of the Lung Cancer PDX Platform at the Icahn School of Medicine at Mount Sinai in New York. Learn more about Dr. Sen.

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Transcript:

Katherine:

Dr. Sen, you are a leading researcher in the field. What is the latest research news that you can share with us about small cell lung cancer?

Dr. Sen:

There’s a lot of great research going on in my lab and labs all across the world. I think for the first time in a very long time, we are really trying to dissect the biology of small cell.   

It has been a research in making for many years. I think we have now really come to a point where we are really trying to understand the disease. I’ll go into a little more about the questions you are trying to answer. So, one of the main questions or one  of the main things that kind of is a hurdle to getting durable treatment options is that the frontline chemotherapy and immunotherapy doesn’t work as well as they should even for the approved regimens, which is the chemotherapy and the immunotherapy.  

The patients often do not have durable benefits. Even if patients have durable benefits, it’s only in a very minority of patient population which means in only about 10 to 15 percent of the total patient population actually do have any benefit from the frontline treatment. So, the main question that we are trying to answer is that why do these patients not respond to immunotherapy and chemotherapy in the frontline.  

What are the mechanisms of resistance to chemotherapy and immunotherapy? Primary resistance, what I mean by primary resistance is that patients who never respond. The disease comes back even while they’re getting the frontline chemo. So, the primary resistance, the mechanisms. Of course, when they have acquired resistance after the maintenance regimen when they come back, why are these patients having this acquired resistance to chemotherapy and immunotherapy? Because only when we understand resistance mechanisms will we be able to then come to the combination strategies.

That’s the next area of research is that once we understand the mechanism of chemotherapy and immunotherapy resistance is then coming up with effective combination therapy. So, what should we combine with immunotherapy in order to make immunotherapy better? I’ll give you an example from the research that we did. 

So, our lab focus is, as I said, on making immunotherapy better. What we understood is that there are certain epigenetic modifiers like LSD1.  

Repressing these, repressing LSD1, with a small molecule inhibitor actually augments or benefits the response to immunotherapy. So now, we are looking at LSD1 inhibitors in combination with immunotherapy. That’s one area that we are focusing on. The second are that we published extensively on is DNA damage response inhibitors which really works in combination with immunotherapy and makes immunotherapy response better.  

Now, we are investigating that in the lab the combination strategies of combining these DNA damage response inhibitors with immunotherapy. So, combination strategies. I think always coming up with novel targets. I will mention there are many novel targets that are right now in the clinical trials actually showing really, really encouraging data.  

I’m talking about DLL3 targeted BiTEs or ADCs we have seen that are showing preliminary data. We have seen a really good really good response in patients. So, finding these targets that are very specific for small cell and that can work in these unique population of patients.  

So, DLL3 targeted agents. There are agents that target B7-H3. So, we are looking at these novel targets and where they could fit in the current therapeutic regimen. Finally, since small cell lung cancer is not a surgical disease, we have to look for other options to find biomarkers. So, liquid biopsy. Liquid biopsy, what I mean by that is understanding the disease not just from tissue but also from blood.  

There’s a lot of research that’s happening in understanding the biology of small cell from blood draws from these patients.  

So, the field of using liquid biopsy or understanding the disease from blood draws is one of the areas that many labs, including ours, are focusing on, and how we can utilize these blood samples to then monitor the disease and also understand the resistance mechanisms to various drugs. I think these are the areas that we are investigating and seems, to me, very important areas that we need to address in order to really manage small cell lung cancer.   

Katherine:

What do these advances mean for small cell lung cancer patients? Are you hopeful?  

Dr. Sen:

Oh, yes. Of course. We’re always hopeful. That’s the goal, right. The goal is to have effective therapies that work and that works for a long time. That also benefits the patients in terms of quality of life which means without very severe adverse effects.   

So, very hopeful. Because I think what was limiting us for all those years for the last 40 to 50 years is that we really did not understand the complexity of small cell lung cancer. It is a very complex disease. It is very different from non-small cell lung cancer which has these mutations that you can target drugs against. So, there are this EGFR mutations and KRAS mutations in non-small cell.  

But small cell, it’s not that. It is not a disease where we have these GATA function mutations that we can devise therapies against. It’s a very different disease. The disease is aggressive. The disease progresses fast, and it also changes its physiology very fast. So, I think for the first time, we really are trying to understand the biology. What that helps is then to come with very informed decisions about therapy.  

So, yeah, I’m very hopeful. Because I think we have now targets that we are actually seeing benefits in patients. I think the more and more we understand resistance mechanisms, we’ll also be able to manage that better.   

Katherine:

That’s very promising news. 

The Role of Antibody Drug Conjugates in Lung Cancer Care

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The Role of Antibody Drug Conjugates in Lung Cancer Care from Patient Empowerment Network on Vimeo.

What are antibody drug conjugates (ADCs)? Expert Dr. Grace Dy defines this new class of therapy and explains how ADCs work to treat lung cancer.

Dr. Grace Dy is Chief of Thoracic Oncology and Professor of Oncology in the Department of Medicine at Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Grace Dy.

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Transcript:

Katherine Banwell:

What is the role of antibody drug conjugates in lung cancer care? 

Dr. Grace Dy:

So, the antibody drug conjugates are an exciting new class of therapy. In fact, it’s been developed for decades, but we had the first antibody drug conjugate that was just approved less than a year ago in lung cancer. And that’s the drug called trastuzumab deruxtecan (Enhertu). It seems like we’re always steps behind our breast cancer colleagues. 

You know, trastuzumab deruxtecan was first developed in breast cancer patients. But hey, we also find we can have some subset of patients who will derive benefit from that. But that’s just one example. There’s plenty of antibody drug conjugates that are being developed. 

So, what are antibody drug conjugates? So, as the name implies, it’s an antibody that is attached to a drug that is actually typically chemotherapy, but you can use any other drug. Generally, it’s a chemotherapy. So, you can think of it as a targeted way of delivering chemotherapy because the antibody is very specific to a certain protein. And generally, what we try to do is look for proteins that are more expressed in cancers than in normal tissues. And you try to target that and improve the therapeutic index by using a more potent chemotherapy and potentially increase efficacy that way.

Emerging DLBCL Treatment Approaches

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Emerging DLBCL Treatment Approaches from Patient Empowerment Network on Vimeo.

What is next for DLBCL treatment? Dr. Jason Westin describes emerging DLBCL treatment approaches.

Dr. Jason Westin is the Director of Lymphoma Clinical Research in the Department of Lymphoma/Myeloma in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Westin, here.

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Transcript:

Katherine:                  

Yeah. You touched upon this earlier, Dr. Westin, but aren’t there emerging DLBCL approaches the patient should know about?

Dr. Westin:                 

Yes. Thankfully, there are many, many. We could spend several hours talking about lots of new therapies coming along. So, it’s a great answer to have. It’s an embarrassment of riches that we have for lots and lots of new therapies that appear quite promising in the early development stage.

In terms of those that have actually crossed over the finished line to be approved by the FDA, we have a handful of new therapies in the past few years that have been approved. Previously, we didn’t really have very many, but now there are multiple therapies that are approved by the FDA outside of a clinical trial, that are targeted treatments.

And those include antibody drug conjugates, basically an antibody like you make against an infection. However, this antibody has a chemotherapy warhead attached to the back of it. So, effectively, it’s a heatseeking missile that finds whatever target we want it to find – in this case, cancer cells – and delivers a high dose chemotherapy right to the bad guys, not to the good guys. There are also other immune therapies that we’ve seen than can be very powerful antibodies, plus immunomodulatory drugs. And we can talk about specific names of these if we’d like.

And then, lastly, there are other oral agents that are coming along that look very promising in terms of their ability to target the cancer cells more directly than growing cells.

Lastly, there’s a very new class of therapies not yet approved, but very promising. I mentioned this before. It’s something called a bispecific antibody. Bispecific – the word bicycle meaning two wheels. Bispecific is two specific antibodies. Basically, it’s an antibody that’s grabbing onto a cancer cell and grabbing onto an immune cell. “I’d like to introduce you guys. Why don’t you guys come in proximity and see if we can have a party.”

And it’s an idea here of trying to get the cancer cell to be attacked by the immune cell simply through this close proximity that occurs. Not yet approved. Looks very promising and I think probably will be approved for multiple different lymphoma types, including large B-cell, in the coming years.

Emerging Approaches in Bladder Cancer Treatment

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Emerging Approaches in Bladder Cancer Treatment from Patient Empowerment Network on Vimeo.

Dr. Shilpa Gupta of the Cleveland Clinic shares a promising update in bladder cancer treatment and research, including the benefits of patient participation in clinical trials. 

Dr. Shilpa Gupta is the Director of the Genitourinary Medical Oncology at Taussig Cancer Institute and Co-Leader of the Genitourinary Oncology Program at Cleveland Clinic. Dr. Gupta’s research interests are novel drug development and understanding biomarkers of response and resistance to therapies in bladder cancer. Learn more about Dr. Gupta, here.

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Transcript:

Katherine:                  

So, Dr. Gupta, are there emerging approaches for treating bladder cancer that patients should know about?

Dr. Gupta:                  

Yes, absolutely. I would say that the field is so rife with so many different treatment approaches and ways to offer more personalized medicine. We know, for example chemotherapy followed by surgery has been the gold standard, but we have seen data that there are certain genes in some patients’ tumors which may predict how well they will respond and potentially we could avoid a life-changing surgery like cystectomy.

And we have trials with immunotherapy adding to chemotherapy in bladder preservation approaches along with radiation. So, these are some of the new work that’s been done. Approaches to intensify the effect of BCG in newly diagnosed non-muscle invasive bladder cancer patients are also ongoing. Then, in the metastatic setting, we have so many treatment options that have become approved in the last couple of years, now the goal is, well, how to sequence the therapies best for the patient and whether in the front-line therapy we can actually get rid of chemotherapy.

Some of these antibody drug conjugates and immunotherapy combinations are proving to be very effective and the hope is that one day patients may not need chemotherapy because we have chemo-sparing regimens. So, there’s a lot going on and I think the progress has been tremendous in the past few years.                                            

Katherine:                  

Some patients may be fearful when it comes to clinical trials. So, what would you say to someone who might be hesitant to consider participating in one? 

Dr. Gupta:                  

I would say there’s a lot of misconceptions out there that going on a trial is like being a guinea pig or you get a placebo. For the most part, patients are getting active drugs whenever possible. The only time where we have placebo-controlled trials is if, for that particular setting, there is no approved treatment. But I think patients should get all the information from their doctors and the study teams about the pros and cons.

Many times, it’s about – you could do the study because the patients meet the criteria and are fit to do it and if they wait for later, they may not be eligible anymore for whatever reasons.

I always put it this way, that standard of care therapies will still be available, but studies are sometimes with a tight window and tight criteria. So, I think patients should know that all these studies that are out there are very ethical and use the best possible control arm. So that even if they don’t get that experimental drug, they still get what is the standard of care unless it is something really being compared to nothing.    

Understanding Common Bladder Cancer Treatment Side Effects

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Understanding Common Bladder Cancer Treatment Side Effects from Patient Empowerment Network on Vimeo.

Dr. Shilpa Gupta of the Cleveland Clinic reviews the most common side effects of bladder cancer therapies.

Dr. Shilpa Gupta is the Director of the Genitourinary Medical Oncology at Taussig Cancer Institute and Co-Leader of the Genitourinary Oncology Program at Cleveland Clinic. Dr. Gupta’s research interests are novel drug development and understanding biomarkers of response and resistance to therapies in bladder cancer. Learn more about Dr. Gupta, here.

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Transcript:

Katherine:                  

I imagine side effects vary among patients. What side effects should someone undergoing treatment be aware of?

Dr. Gupta:                  

Yeah, and that also depends on what kind of treatment they’re getting, Katherine. So, if somebody’s getting chemotherapy, some of the usual chemotherapy related side effects.

Again, it depends on what chemotherapy they are getting, but usually it’s nausea, vomiting, peripheral neuropathy, hair loss, low count, so we try to prevent their counts from going down to prevent infection. If they’re undergoing a local therapy like BCG, they may get irritation in the bladder, something called urinary tract infections can happen, or just an inflammatory state.

Immunotherapy is not as hard as chemotherapy, any day it’s easier but it can cause some rare and infrequent side effects because the immune system can turn against other organs which can sometimes be life threatening or fatal. That could be inflammation of the lung, of the colon, of the different organs in the brain, of the thyroid gland, of muscles, of heart. It can be pretty much anything. We educate the patients accordingly for that.

And, as far as the newer antibody drug conjugates are concerned, they can cause neuropathy or low counts, hair loss. So, every treatment depending on what treatment we’re choosing has a different treatment side – related toxicity profile and we go about reducing or modifying doses as we go along treating the patient.

Current Treatment Approaches for Bladder Cancer

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Current Treatment Approaches for Bladder Cancer from Patient Empowerment Network on Vimeo.

Dr. Shilpa Gupta provides an overview of available bladder cancer treatment approaches and discusses the factors that impact therapy decisions.

Dr. Shilpa Gupta is the Director of the Genitourinary Medical Oncology at Taussig Cancer Institute and Co-Leader of the Genitourinary Oncology Program at Cleveland Clinic. Dr. Gupta’s research interests are novel drug development and understanding biomarkers of response and resistance to therapies in bladder cancer. Learn more about Dr. Gupta, here.

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Transcript:

Katherine:                  

You’ve touched upon treatment options but let’s walk through the treatment approaches for bladder cancer and who they might be right for, and I’d like to start with surgery. Who would be a good candidate for surgery?

Dr. Gupta:                  

I think patients who are otherwise fit, that is, they have good performance status, don’t have a lot of cardiac or other comorbidities, are not very obese, and of course have to be fit for any major procedure are usually considered good surgical candidates. But, as far as – In terms of staging, the patients with stage I, if BCG does not work in them or immunotherapy doesn’t work, they are recommended surgery if they are good candidates.

If they are not good candidates, we then – our role as medical oncologists is to offer other systemic therapies. As far as stage II cancer is concerned, the gold standard has been chemotherapy, followed by surgery but that’s the gold standard.

It may not apply for every patient. Depending on how fit patients are. Are they – we don’t usually just go by their chronological age but how fit they are? What are their comorbidities? If surgery is going to be a big burden for them moving forward, then we do talk about radiation and chemotherapy and other bladder preservation approaches.

Katherine:                  

What about immunotherapy and targeted therapies? Who would you use those on?

Dr. Gupta:                  

Well, since the advent of immunotherapies back in 2016 they’ve really – we’ve made a lot of progress and changed the way treat bladder cancer and the overall survival has improved by leaps and bounds with all these drugs.

Immunotherapy now plays a role in different stages. It is approved for superficial or non-muscle invasive bladder cancer if, let’s say, BCG doesn’t work. In muscle invasive disease we have along with others shown that immunotherapy is safe and effective, although it is not yet FDA approved, so there is a lot of clinical trials going on to prove its superiority in combination and by itself.                                   

And, in metastatic disease or locally advanced disease immunotherapy plays a huge role for patients who have either disease recurrence after chemotherapy or are not good candidates for any chemotherapy.

I would say that immunotherapy is a very big – plays a very big role in the treatment. Unfortunately, not everybody responds to immunotherapy only about 20 to 25 percent of patients do.

 That’s why we have these other novel therapies that have been coming through, like antibody drug conjugates, namely enfortumab vedotin, sacituzumab govitecan, and targeted therapy in the form of an FGFR inhibitor was the first targeted therapy that was approved a couple of years ago for patients who have a mutation in their tumors.

That’s really personalized medicine for those patients.

Katherine:                  

Right. What about biomarker testing? Does the presence of certain biomarkers impact certain treatment options?

Dr. Gupta:                  

That’s a great question and we’re all striving to find the perfect biomarker in bladder cancer. In the past we thought that expression of PD-L1 in the tumor cells and immune cells is a marker of how well the immunotherapy will work, but we have learned over the past couple of years that biomarker has turned out to be quite useless.

We don’t really need that to guide our treatment. We’re still depending on clinical biomarkers for immunotherapy use or chemotherapy use. I would say that the biomarker question is still being looked at and eventually I would say it’s not going to be one biomarker, but a composite of several different biomarkers that we will be able to use comprehensively.