Tag Archive for: Avastin

Essential Genetic Testing for Personalized Gynecologic Cancer Treatment

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How important is genetic testing for gynecologic cancer? Expert Dr. Ramez Eskander from UC San Diego Health discusses the role of genetic testing in gynecologic cancer care – including molecular tumor testing, germline testing, HRD tests, and BRCA mutations – along with proactive patient advice. 

[ACT]IVATION TIP

“…every patient with ovarian cancer needs to know their BRCA status and needs to know their molecular tumor testing status. Feel empowered to ask these questions. It is data that you should have at hand as you make informed decisions.”

See More from [ACT]IVATED Ovarian Cancer

Related Resources:

Optimizing Ovarian Cancer Care: Genetic Testing and Treatment Approaches

Optimizing Ovarian Cancer Care: Genetic Testing and Treatment Approaches

 PARP Inhibitors in Ovarian Cancer Treatment: Understanding Side Effects

PARP Inhibitors in Ovarian Cancer Treatment: Understanding Side Effects

 What Are Common Symptoms of Ovarian Cancer

What Are Common Symptoms of Ovarian Cancer?

Transcript:

Lisa Hatfield:

Dr. Eskander, for patients newly diagnosed with a gynecologic cancer, how important is it to get genetic testing like HRD or homologous recombination deficiency, and how can understanding one’s genetic profile help them and their care team choose the best treatment?

Dr. Ramez Eskander:

This is an incredibly important question. It is pivotal that every newly diagnosed ovarian cancer patient have germline genetic testing and molecular tumor testing because of the impact it can have on their treatment strategy, independent of course, the importance of them being diagnosed. So that if they had a genetically inherited mutation, we call it germline mutation, their relatives can be informed and tested, so they can have risk reducing surgical interventions.

In the ovarian cancer setting, homologous recombination deficiency testing is crucial, because it helps inform the magnitude of benefit that we might see with treatment strategy, in this case, combination of PARP inhibitor plus bevacizumab (Avastin) or PARP inhibitor alone. So these treatment strategies have been proven to improve clinical outcomes. And knowing HRD test status and knowing whether you have a germline mutation is pivotal to putting context around a conversation surrounding maintenance treatment approaches. And understanding the profile is what drives your ability to make an informed decision about your maintenance treatment strategies.

And it can be quite nuanced. For example, if a patient is HRD test-negative, they would have to make a decision about what kind of maintenance therapy with their provider. Do I do maintenance treatment? Should I do bevacizumab alone? Should I do a PARP inhibitor alone? And what might I anticipate with either of these approaches, and what are the pros and the cons? And an HRD test-positive patient, there is clear data supporting the use of PARP inhibitors or PARP inhibitors plus bevacizumab in combination.

So you want to be informed of those data as you look to make a decision. And this to me is germane to the care of patients with ovarian cancer. Every patient should know their status and in a similar manner when we talk about endometrial cancer, I would just like to elaborate that it’s critical to know what is the finding of the testing on the tumor for the endometrial cancer? Is this a mismatch repair-deficient or mismatch repair-proficient endometrial cancer and testing that was done? 

Lisa Hatfield:

That’s a lot of information. So I just want to clarify a couple of comments that you made. So when you talk about the germline testing of germline mutations, that has to do with mutations that are present in a patient’s, all the cells in a patient’s body. Is that correct? So like the BRCA1 and 2 genes?

Dr. Ramez Eskander:

That’s correct.

Lisa Hatfield:

And then there are the other types of mutations, some people call them somatic mutations that are just have to do with the DNA sequencing of the actual tumor or cancer cells. So is HRD then, is that a germline mutation, or is that more of a somatic?

Dr. Ramez Eskander:

Perfect question. So HRD itself isn’t a mutation. HRD is looking at changes in the tumor DNA, but you bring up a perfect point. A germline mutation is inherited, meaning that it is in every cell, and it’s a predisposition and increase in cancer risk. Somatic mutations are not inherited. Somatic mutations are mutations in the tumor unique to that cancer. That’s why we talk about informing your family or relatives with a germline mutation, because that was inherited. And other people in the family may have the same inherited mutation. Somatic mutations are not inherited. They arise in the cancer, and they require tumor testing to inform.

Homologous recombination deficiency isn’t looking for a specific mutation, but it’s rather examining the tumor DNA to look for something we call genomic scarring. The analogy I gave is if I’m driving on the freeway and I’m stuck in traffic, I know that I’m stuck in traffic, but I don’t know exactly why. Is there construction on the freeway? Is there an accident? It’s unclear. So the HRD is looking at the genomic signature, and it needs tumor samples to do that, but it’s not honing in on a specific mutation.

I know it can get a little bit complicated. I’ll just add this, A patient who has a germline BRCA mutation, if you test their tumor, the near vast majority are going to have an HRD test-positive signature, because it drives that. So that’s like saying, I know the reason that there’s that genomic instability, it’s a BRCA mutation, but there are patients we call beyond BRCA. There are many things that may cause this independent of BRCA that we may not know of right now, but we can identify the genomic scar, and that qualifies patients as having a homologous recombination deficiency test-positive tumor. 

So my tip is every patient with ovarian cancer needs to know their BRCA status and needs to know their molecular tumor testing status. Feel empowered to ask these questions. It is data that you should have at hand as you make informed decisions.

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PARP Inhibitors in Ovarian Cancer Treatment: Understanding Side Effects

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Ovarian cancer treatment may cause side effects, so what should patients be aware of? Expert Dr. Ramez Eskander from UC San Diego Health discusses common ovarian cancer treatment side effects, management of side effects, and proactive patient advice for optimal care. 

[ACT]IVATION TIP

“…make sure you’re asking appropriate questions, that you’re educated about treatment-related side effects as they relate to PARP inhibitors. And then lastly, to understand that dose interruptions or dose reductions are an expected part of treatment with really any anti-cancer directed therapy, including PARP inhibitors, with a goal to keep patients on therapy, because they’re benefiting from this treatment.”

See More from [ACT]IVATED Ovarian Cancer

Related Resources:

Optimizing Ovarian Cancer Care: Genetic Testing and Treatment Approaches

Optimizing Ovarian Cancer Care: Genetic Testing and Treatment Approaches

 Essential Genetic Testing for Personalized Gynecologic Cancer Treatment

Essential Genetic Testing for Personalized Gynecologic Cancer Treatment

 What Are Common Symptoms of Ovarian Cancer

What Are Common Symptoms of Ovarian Cancer?

Transcript:

Lisa Hatfield:

Dr. Eskander, what are some common side effects of ovarian cancer treatments, particularly with long-term use of PARP inhibitors, and how can patients manage these side effects and maintain their quality of life during treatment?

Dr. Ramez Eskander:

PARP inhibitors, Lisa, are a very important part of the management of patients with advanced stage ovarian cancer. They have become a commonly used treatment in the first line we call it therapy or when patients are initially diagnosed as a maintenance treatment strategy and those PARP inhibitors can be given alone or the PARP inhibitors can be given in combination with another drug called bevacizumab (Avastin) as maintenance therapy. PARP inhibitors is a class I like to say are drugs that can be well tolerated.

One of the most important things that we face as providers is we are responsible to make sure our patients are educated. When we are able to have a conversation with a patient and educate them about potential treatment-related side effects and they feel empowered in managing those side effects, we’re able to make sure that patients can stay on treatment, tolerate, and of course, most importantly, benefit from this study-directed therapy for management of their cancer. As a class, some of the more common side effects of PARP inhibitors are fatigue. It’s actually one of the most common side effects.

We can see gastrointestinal side effects. They can be varied, but it can be constipation or diarrhea or abdominal cramping. We can also see hematologic side effects, which means impact on the blood counts. It can cause anemia, lowering the red blood cell count, lowering the white blood cell count, and in some instances, lowering the platelet count. There are rare, when I say rare in the front line, if you look across trials, less than about 1-1/2 percent of patients can develop a secondary malignancy of the bone marrow that’s called myelodysplastic syndrome or acute myeloid leukemia. Those are very uncommon, but they have been described when we use PARP inhibitors as a maintenance strategy in the front line.

So in these circumstances, again, it’s about education. It’s about making sure that you’re asking your provider, what might I experience, and how are we going to be proactive about mitigating these side effects? And I would like to emphasize that it’s okay when needed, to have a dose interruption, meaning pause the medication for a period of time, or a dose reduction, reduce the dose.

Because by doing so, we can make sure that a patient can stay on a treatment that they tolerate. And so managing these side effects is multi-pronged. It’s your clinician, your treatment team, of course, because it goes beyond the clinician who’s caring for you. It’s about understanding that an interruption in treatment may be needed, or reduction in the dose may be required, because that helps us keep patients on treatment. 

Lisa Hatfield:

So if I understand correctly then, PARP inhibitors are something that a patient remains on until disease recurrence. That’s not a limited duration therapy, but it can be interrupted if needed a little bit of a break. So is that correct that it’s until disease recurrence?

Dr. Ramez Eskander:

In the front line when we’re talking about maintenance treatment strategy with PARP inhibitors, there’s actually a defined time period, but that defined time period is quite long on the order of two years. So you’re on a medication for a long period of time. Now, if you get to that two years, and thankfully there’s no evidence of cancer recurrence or active disease, you may be able to discontinue the PARP inhibitor.

The different trials had different durations of maintenance therapy. So you can imagine that there can be some fluctuation between trials two years or three years. But needless to say, it’s still a long period of time that you’re on an anti-cancer directed maintenance therapy. When you get to the end of that, however, you would be able to potentially discontinue treatment in conversation with your provider.

So here, in my opinion, the [ACT]IVATION tip is make sure you’re asking appropriate questions, that you’re educated about treatment-related side effects as they relate to PARP inhibitors. And then lastly, to understand that dose interruptions or dose reductions are an expected part of treatment with really any anti-cancer directed therapy, including PARP inhibitors, with a goal to keep patients on therapy, because they’re benefiting from this treatment.

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Optimizing Ovarian Cancer Care: Genetic Testing and Treatment Approaches

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What’s vital for ovarian cancer patients to know about treatment options and approaches? Expert Dr. Ramez Eskander from UC San Diego Health discusses chemotherapy, surgery, the importance of molecular testing, treatment approaches for optimal outcomes, and proactive patient advice. 

[ACT]IVATION TIP

“…ask the questions of your provider. Understand, did you have genetic testing? Did you have molecular tumor testing? And do the results of that genetic or molecular tumor testing impact the treatment recommendations for maintenance therapy? I want to make sure everybody feels empowered to ask those questions and have those answers.”

See More from [ACT]IVATED Ovarian Cancer

Related Resources:

PARP Inhibitors in Ovarian Cancer Treatment: Understanding Side Effects

PARP Inhibitors in Ovarian Cancer Treatment: Understanding Side Effects

 Essential Genetic Testing for Personalized Gynecologic Cancer Treatment

Essential Genetic Testing for Personalized Gynecologic Cancer Treatment

 What Should Ovarian Cancer Know About Immunotherapy and Targeted Therapies

What Should Ovarian Cancer Know About Immunotherapy and Targeted Therapies

Transcript:

Lisa Hatfield:

Dr. Eskander, for someone who is newly diagnosed with ovarian cancer, what are the most common treatment options available, and how can patients know which treatment plan is best suited for their specific situation?

Dr. Ramez Eskander:

Newly diagnosed ovarian cancer is managed utilizing chemotherapy and surgery. The order can vary depending on the specific patient, how they present, their cancer burden, whether you receive chemotherapy, surgery, followed by chemotherapy, or surgery and chemotherapy. The drugs, the backbone of treatment, are very similar, that is, two chemotherapy drugs called carboplatin (Paraplatin) and paclitaxel (Taxol). I will say that there are other drugs used in the front line. Another drug that’s commonly used is a drug called bevacizumab or Avastin. This is called an anti-angiogenic drug.

And we’ve also identified biomarkers that have really transformed front-line management. Any and every newly diagnosed ovarian cancer patient should have genetic testing because about 15 percent of ovarian cancers can have a genetic predisposition, meaning that you’ve inherited a gene that increased your risk of developing the cancer. And that’s critically important for the treatment of that patient, but also for any family members who would benefit from what we call cascade genetic testing, they would get tested. And if they were identified to have the gene, they could be followed and have risk-reducing surgery.

The reason this molecular testing of ovarian cancer and again, every patient should have genetic testing and molecular testing is critically important is it is informing maintenance treatment strategies. We’ve now conducted several clinical trials that show the utilization of a class of drug called PARP inhibitors. These are oral pills. When we use these medications in patients who have a BRCA mutation, there is a dramatic improvement in clinical outcome.

So every advanced stage ovarian cancer patient should be tested. And for those who have a BRCA mutation, every one of those patients should be treated with a maintenance PARP inhibitor. And maintenance meaning after you finish the chemotherapy drugs that I mentioned, you go on to that maintenance PARP inhibitor. And we’ve also had clinical trials that have expanded that opportunity, because not only are we looking at patients that have a BRCA mutation, but we’ve now expanded and incorporate into patients who are homologous recombination-deficient, or HRD test-positive.

Because studies have shown that when you give the PARP inhibitors in combination with bevacizumab, the drug that I alluded to a moment ago, you can again get a very significant improvement in clinical outcome including an improvement in overall survival. So biomarker testing, genetic testing, chemotherapy plus surgery is a backbone but importantly utilizing that molecular testing to inform maintenance treatment strategies which have clearly improved clinical outcomes, and these are all very critical conversations to have with the physician who’s taking care of you.

And for me, my [ACT]IVATION tip here is ask the questions of your provider. Understand, did you have genetic testing? Did you have molecular tumor testing? And do the results of that genetic or molecular tumor testing impact the treatment recommendations for maintenance therapy? I want to make sure everybody feels empowered to ask those questions and have those answers.

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Lung Cancer: Donna’s Clinical Trial Profile

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Lung Cancer: Donna’s Clinical Trial Profile from Patient Empowerment Network on Vimeo.

Lung cancer patient Donna had a sub-optimal experience with her first treatment regimen. Watch as she shares her lung cancer journey, knowledge and benefits gained from a clinical trial, and her advice to patients seeking additional treatment options.

Patient-to-Patient Diverse Lung Cancer Clinical Trial Profiles

Transcript:

Donna: 

I’m Donna, I am 68 years old, and I was diagnosed with lung cancer in 2012. 

When I was first diagnosed with lung cancer, I was put on a regimen of paraplatin (Carboplatin) and bevacizumab (Avastin) drugs. I received that for four or five months and did not do particularly well on it.  My body did not react well to those chemicals, my tumors, however, did respond as long as I was getting the drug. 

After we discovered that my tumors were not going to respond to chemo unless I was getting it all the time, my doctor suggested that I either go on another drug, chemo drug that was even harsher than what I had been on and did not have as good of results or suggested that I might do a clinical trial. I had been told that I probably only had about four months to live. And I decided that, number one, I was in no hurry to be sicker than I already was and number two, that if there was a way I could help future patients by participating in a trial that the trial was the way I wanted to go. I never ever assumed that I would benefit from being in a clinical trial, I was very uninformed about clinical trials. 

A clinical trial is a way that the pharmaceutical company or researchers test certain drugs. They will see if the drug works at all, it moves to humans and out of the laboratory, and everything doesn’t necessarily work the same way or on humans as it did in the lab. So…in the Phase III trial like I was in, by that point in time, they’re learning how in the fairly general population, how the drug is going to react, if it’s actually going to work, how much of a dose is the right dose, and how frequent it should be. The clinical trial is just to provide the information that’s needed to determine whether a drug should go forward into the general population or not.  

One tumor started growing again, and I chose to have radiation, which made me have to get out of the clinical trial. But after radiation, I went back onto the same drug that we had been testing through the clinical trial, because I had responded so well through it, and I stayed on that drug until from 2013 until 2019. And during in April of 2019, I quit having any kind of treatments, and so now I’m just monitored every four months to make sure that my tumors have remained stable and so far, so good. 

I would go into a clinical trial without hesitation if my tumors begin to grow again, my first consideration will be to get into another clinical trial, you are getting the cutting-edge drug. And not only that, while I was in the clinical trial, I had a researcher and I had my oncologist, I had a lot of people really following my health. I had multiple, far more scans done, which some people might look at as a negative, but they were really following me closely to make sure that my response was what it needed to be. You can get out of the clinical trial, you are not stuck in a clinical trial. So, if you get into it and you are either sick or if your tumors are not responding the way you hope they would, you’re not stuck in a clinical trial, and that’s an important thing to know. To me, there will never be another option that I will consider first, I will always consider the clinical trial first. And because I felt that the quality of care I got was higher, and it also saves you a lot of money because at least the drug itself is going to be provided at no cost. 

So that’s a huge consideration too. 

I would not be afraid to look into clinical trials, I would never accept a doctor telling me that there were no options for me. I have friends who had doctors tell them that they just didn’t think there was anything more that could be done, they needed to go into hospice. My advice is to look for a different doctor, because that’s not always true. And clinical trials are not necessarily easy to find, but I would certainly do my due diligence and look into whether there is one that’s good for you. And I would also strongly recommend that you immediately go through genetic testing so that you know what kind of mutations you might have, because that will drive the kind of clinical trial you might be wanting to get into, and also just the treatment in general.