How Do Biomarkers Impact Ovarian Cancer Treatment and Care?

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How do biomarkers impact ovarian cancer care? Dr. Heidi Gray discusses how genetic biomarkers like BRCA-1, BRCA-2, and HRD inform treatment options, affect prognosis, and guide therapies like PARP inhibitors. 

Dr. Heidi Gray is the Division Chief of Gynecologic Oncology and the Director of Gynecologic Oncology Clinical Trials at UW Medicine. Learn more about Dr. Gray.

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Transcript:

Katherine Banwell:  

What are the most common biomarkers associated with ovarian cancer? 

Dr. Heidi Gray:  

So, the most common biomarkers, first of all, are the genetic mutations that are associated with higher risk. So, many folks are familiar with BRCA-1 and BRCA-2. There are a couple of lesser-known genetic mutations that fall into that family that also can put patients at an inherited risk. 

Other biomarker testing that we do is for something called HRD, which is a test to look at a profile of the cancer that is similar to having the BRCA-1 and BRCA-2 mutations. It is a spectrum of different testing that may make those cancers more susceptible to PARP inhibitor therapy.  

Katherine Banwell:  

Are there biomarkers associated with prognosis? 

Dr. Heidi Gray:  

Let me back up a little bit. So, the biomarkers associated with prognosis – yes. So, in patients who have BRCA-1 or BRCA-2 mutations, they actually tend to have better prognosis longer term and better responsiveness to chemotherapy and other therapies. 

Patients who also have HRD may also have a little improved responsiveness to some of the therapies as well.  

Katherine Banwell:  

How do these biomarkers impact ovarian cancer treatment options? 

Dr. Heidi Gray:  

Good question. So, the biomarker testing again, particularly for the BRCA-1, BRCA-2, and then the HRD spectrum, there have been several very large studies that have looked at using a variety of drugs that fall under this group called PARP inhibitors, P-A-R-P inhibitors.  

These drugs specifically target cancers that have these mutations – or more susceptible to these mutations and interestingly have found that when we use these PARP inhibitors in a maintenance therapy, so after patients have completed their primary treatment, surgery, chemotherapy, and then go on maintenance therapy to prevent recurrence, they have very, very long improvement in survival and pushing out recurrence very far, significantly so, more than we’ve seen for anything in ovarian cancer in recent years.   

So, it’s very, very exciting. 

Katherine Banwell:  

What question should patients ask about test results?  

Dr. Heidi Gray:  

It is interesting now because as many patients have experienced, they sometimes get their test results before their provider has had a chance to review them as part of the patient access program that has been in place. So, I find that many patients have had time to sit with their results or question or go on the Internet about them before they see me. So, some of it is helping direct, okay, where are you getting your information from and all of that, because I think that that is something newer now. 

But I think it’s important for patients to be asking do I qualify for genetic testing, what are those results, what are the implications for myself and/or my family members? Then the molecular testing, as I said, is a very important next step that we do recommend for all, certainly advanced ovarian cancers or recurrent ovarian cancers, to help better guide therapy. 

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.”

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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.”

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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.”

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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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Ovarian Cysts and Uterine Fibroids: Is There a Connection to Ovarian Cancer?

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Ovarian Cysts and Uterine Fibroids: Is There a Connection to Ovarian Cancer? from Patient Empowerment Network on Vimeo.

Are ovarian cysts and fibroids a concern for ovarian cancer patients? Expert Dr. Ebony Hoskins shares her perspective about fibroids and cysts, what she looks for in patients, and her advice to patients to ensure their best care.

Dr. Hoskins is a board-certified gynecologic oncologist at MedStar Washington Hospital Center and assistant professor of Clinical Obstetrics and Gynecology at Georgetown University Medical Center. Hoskins sees women for gynecological malignancies, which include the treatment of endometrial, ovarian, vulva, vaginal and cervical cancers.

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Transcript:

Mikki:

Okay, Dr. Hoskins, are fibroids or ovarian cysts related to ovarian cancer?

Dr. Ebony Hoskins:

So from a gynecologic oncology standpoint, when I see someone who has a documented uterine fibroid, I don’t think that it’s related to ovarian cancer. Certainly when I see a woman that has ovarian cysts, that’s something that potentially could be an ovarian cancer. But then I’m looking at whether it’s a cyst, whether there’s fluid. So there’s other characteristics in the imaging that I have obtained. So I think the question is, are fibroids and ovarian cysts related to ovarian cancer? Not really, but I think it’s important that we are basing this on some objective data, right? So I can press on someone’s belly and say, “Oh, that’s fibroids.” But asking my activation tip would say, “Hey can I get an ultrasound to look at my pelvic organs?” Not just randomly, but if you, if a patient feels like it’s fibroids, let’s prove it, let’s get an ultrasound. And that will look not only at the uterus, it looks at the adnexa, which is the fallopian tubes and the ovaries, and have an objective diagnosis for what’s going on in the GYN organs and pelvis.

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Sexual Health After a Cancer Diagnosis: An Expert Weighs In

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Sexual Health After a Cancer Diagnosis: An Expert Weighs In from Patient Empowerment Network on Vimeo.

What can ovarian patients do if they have sexual health issues that arise during their patient journey? Expert Dr. Ebony Hoskins explains issues that may come up for some patients and patient advice on how to seek support. 

Dr. Hoskins is a board-certified gynecologic oncologist at MedStar Washington Hospital Center and assistant professor of Clinical Obstetrics and Gynecology at Georgetown University Medical Center. Hoskins sees women for gynecological malignancies, which include the treatment of endometrial, ovarian, vulva, vaginal and cervical cancers.

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Transcript:

Mikki:

Dr. Hoskins, can you speak to the sexual health following a cancer diagnosis, and which healthcare team member should patients have a conversation with?

Dr. Ebony Hoskins:

I think this is a great question. I think sexual health is something that goes undiscussed unless we ask it, and I think sometimes it’s uncomfortable for the patient, it’s uncomfortable for the provider. But I do talk to a lot of women that have decreased libido or pain, or there’s a lot of dysfunction sometimes after surgery or chemotherapy, and some of it is related to the actual treatment itself. Physiologic meaning how the body functions after treatment, and some could be the fact that there is shame associated with that, sometimes the cancer is involving a sexual organ in that area, and so I think bringing discussion up to your…whether the provider is a gynecologic oncologist and is the person who did the surgery, or the who person gave the chemo or the radiation oncologist. Also, there are mid-level providers who do survivorship, and it just kind of depends on who’s taking care of you after completion of treatment, butI know there are survivorships, and these are times to bring it up. Bring it up to your provider, number one, and they may have resources to refer you to in terms of getting through these difficult times, because I think ultimately you can get your sexual life back. 

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Ovarian Cancer and Clinical Trial Participation: What Patients Should Know

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Ovarian Cancer and Clinical Trial Participation: What Patients Should Know from Patient Empowerment Network on Vimeo.

What do ovarian cancer patients need to know about clinical trial participation? Expert Dr. Ebony Hoskins explains the importance of clinical trial participation and key advice for patients who are considering participation in a clinical trial.

Dr. Hoskins is a board-certified gynecologic oncologist at MedStar Washington Hospital Center and assistant professor of Clinical Obstetrics and Gynecology at Georgetown University Medical Center. Hoskins sees women for gynecological malignancies, which include the treatment of endometrial, ovarian, vulva, vaginal and cervical cancers.

[ACT]IVATION TIP

“…inquire with your doctor, ‘Am I a candidate for a clinical trial? Do you offer a clinical trial, are there clinical trials that would fit my scenario that’s local that I could go to? Are there clinical trials that are available, say, out of state that you think I will be a good fit for?’”

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Transcript:

Mikki:

Dr. Hoskins, why is clinical trial participation so important in ovarian cancer, and what advice do you have for patients considering a clinical trial?

Dr. Ebony Hoskins:  

One, I always tell patients is the reason we know what to give you now, treatment is based off a clinical trial. So we need these trials. We didn’t just create a new drug and just gave it. We need to know, is it going to improve survival? What are the side effects? Is it going to kill the cancer? And so it’s important to be on the cutting edge if you will, of advancement in the field. The only way I know what to give patients is based off a clinical trial.

Right, so that’s number one. The advice for patients I have is, I think understanding what the options are for treatment, whether they come off of trial. So knowing if I’m not on trial, what am I going to get? If I am on trial, what am I going to get? What are the side effects? Side effects is an important thing. What are the safety issues? Because not only are there side effects, there can be a safety issue. I think one thing that we don’t really talk about that could be there, is some of the clinical trials depends on who’s sponsoring it, provide the drugs, and some of the drugs are quite costly, so that’s something that we’re not talking about.

The financial toxicity and sometimes coming under their trial, the drugs are covered, so you’re getting cutting-edge care that comes as maybe it’s not as costly to you, so I think, again, my activation tip for a patient is inquire with your doctor, “Am I a candidate for a clinical trial? Do you offer a clinical trial, are there clinical trials that would fit my scenario that’s local that I could go to? Are there clinical trials that are available, say, out of state that you think I will be a good fit for?” And sometimes…again, not every patient is a clinical trial candidate for a number of reasons, but asking the question, I think is huge.

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What Should Ovarian Cancer Patients Know About Immunotherapy and Targeted Therapies?

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What Should Ovarian Cancer Patients Know About Immunotherapy and Targeted Therapies? from Patient Empowerment Network on Vimeo.

What do ovarian cancer patients need to know about immunotherapy and targeted therapy? Expert Dr. Ebony Hoskins explains how immunotherapy and targeted therapy are used, research about them, and advice to patients.

Dr. Hoskins is a board-certified gynecologic oncologist at MedStar Washington Hospital Center and assistant professor of Clinical Obstetrics and Gynecology at Georgetown University Medical Center. Hoskins sees women for gynecological malignancies, which include the treatment of endometrial, ovarian, vulva, vaginal and cervical cancers.

[ACT]IVATION TIP

“…asking ‘Has my tumor been studied, or has there been any sequencing to determine if they are a candidate for targeted therapy?’”

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Transcript:

Mikki:

Dr. Hoskins, what is the role of immunotherapy or targeted therapy in ovarian cancer care?

Dr. Ebony Hoskins:

So the role of immunotherapy, I think is still kind of ongoing. We’ve seen some improvements with endometrial cancer, not so much the same with ovarian cancer. In terms of targeted therapy, there are new drugs that are coming out that are targeting a different molecular markers in the actual tumor that are now offered for patients with ovarian cancer. And that’s been shown to be proven to work and improve the response and survival. My activation tip, particularly for patients who are affected by ovarian cancer, is asking, “Has my tumor been studied, or has there been any sequencing to determine if they are a candidate for targeted therapy?”

Mikki:

Thank you.

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