Exploring Your Ovarian Cancer Care Options: How Testing Helps Personalize Treatment

Katherine Banwell:

Hello and welcome. I’m your host, Katherine Banwell. This webinar is part of the Patient Empowerment Network’s INSIST! series. Today, we’re joined by an ovarian cancer specialist who will explain the important role of testing and how results may impact care and treatment options for patients. Before we meet our guest, though, let’s review a few important details. The reminder email you received about this program contains a link to a program resource guide. If you haven’t already, click that link to access information to follow along during the webinar.

At the end of the program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today in order to help us plan future webinars. And finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Okay, let’s meet today’s guest. Joining us is Dr. Kevin Elias. Dr. Elias, welcome. Would you please introduce yourself?

Dr. Kevin Elias:

Absolutely. Thank you so much for having me. So, I’m Kevin Elias. I’m a gynecologic oncologist at the Cleveland Clinic with a special focus on ovarian cancer in my practice.

Katherine Banwell:

Thank you so much for taking the time to join us today. Before we get into learning more about essential testing, let’s find out more about you. How did you become an ovarian cancer specialist, and what’s your area of focus?

Dr. Kevin Elias:

Absolutely. So, I became interested in ovarian cancer, in particular, because I also run our research laboratory at the Cleveland Clinic. And I came to Cleveland about two years ago, specifically to expand the translational research program within ovarian cancers.

That means understanding the causes of ovarian cancer, as well as developing new strategies for novel therapies.

Katherine Banwell:

Okay. Thank you for that. So, before a treatment is decided on, it’s important to know more about a patient’s individual diagnosis. Let’s start with how is ovarian cancer staged?

Dr. Kevin Elias:

Absolutely. Ovarian cancer is staged based on whether it’s confined to the fallopian tube in the ovary, or whether it’s involving other structures in the pelvis or distantly elsewhere in the body. Most ovarian cancers, when they’re diagnosed, will be stage III or stage IV, meaning that there’s cancer that has spread beyond just the ovary and immediately localized structures, but to other sites within the abdominal cavity or elsewhere in the body.

Katherine Banwell:

And why are you saying it’s usually only stage III and IV?

Dr. Kevin Elias:

So, unfortunately, most women with ovarian cancer don’t become symptomatic to the point where they’re diagnosed until they already have disease that’s spread to other parts of the body.

Katherine Banwell:

Yeah. What testing should be done following an ovarian cancer diagnosis?

Dr. Kevin Elias:

So, importantly, ovarian cancer is diagnosed with histology, meaning we need to have tissue under the microscope to make a diagnosis of ovarian cancer. At this time, there’s no blood test or radiologic imaging test, which can be diagnostic of ovarian cancer until we have a biopsy. So, the most important thing is having the tissue looked at, preferably by a gynecologic pathologist with an expertise in ovarian cancer.

At the time that the tissue was looked at, we would want to compare it with blood markers, particularly a CA-125 test or CA-125 test, which is a protein that helps guide treatment for women who’ve been diagnosed with ovarian cancer. And then, we would want the pathologist to start to look at particular markers, which I imagine we’ll talk about in a minute, that might be expressed by a tumor, which might help guide individualized therapy.

Katherine Banwell:

When you refer to getting a tissue from a patient, does that involve a biopsy?

Dr. Kevin Elias:

It depends on where the disease is distributed.

So, for patients who are not going to be going directly to surgery, a biopsy would be preferable. And that can be done either by an interventional radiologist through a needle biopsy, or it can be done by a surgeon using a small surgical procedure called a laparoscopy, or we look in with a camera and use that to direct the biopsy directly. If there’s not evidence of cancer outside of the ovary, or it seems like the amount of disease that’s there would be amenable to complete removal of it surgically, it’s preferable to go directly to surgery rather than to do a biopsy first.

Katherine Banwell:

What testing should be done following an ovarian cancer diagnosis?

Dr. Kevin Elias:

So, once a woman has been established to have ovarian cancer, it’s important that we start to subdivide what type of ovarian cancer it is. So, that includes understanding a little bit more about the genetic makeup of the ovarian cancer. We divide ovarian cancers broadly into two groups, what we call homologous repair deficient and homologous repair deficient cancers, or HR-proficient and HR-deficient tumors.

The reason that matters is that patients who have deficient tumors are much more likely to have a type of ovarian cancer that is familial. So, it could put the individual at risk for other cancer types, as well as other individuals in their family at risk for cancer. It also means that those are tumors that are more likely to respond to medications later on in therapy known as PARP inhibitors, as opposed to the proficient tumors in whom those types of therapies are not indicated. And those tumors are also much less likely to be genetic.

Katherine Banwell:

Are there advances in imaging that help guide this process?

Dr. Kevin Elias:

Unfortunately, not so much at the moment. We do have some imaging, particularly at Cleveland Clinic, which we’re starting to use for image-guided surgery. And so, there are certain medications which can be administered at the time of surgery itself to help us identify sites of disease that might not be readily visible to the naked eye. But that would be intraoperative decision-making. Not so much that there’s a difference in the imaging that we might get for preoperative evaluation or the imaging that we might get for post-treatment surveillance for a patient.

Katherine Banwell:

Dr. Elias, why is it so important to get an accurate diagnosis?

Dr. Kevin Elias:

Ovarian cancer can overlap with a lot of other different types of cancer, which can look very similar, both on imaging as well as on blood tests. Whenever we see an individual who has an unspecified cancer process which is involving multiple areas within the abdomen, while it could be an ovarian cancer, it could also be a uterine cancer. It could be a cancer from a gastrointestinal source, such as a colon or pancreatic or stomach cancer. It could even be something like metastatic breast cancer. And so, it’s very important, since the chemotherapy for each one of these medications is different, that we have an accurate diagnosis.

Katherine Banwell:

What questions, then, should patients ask about their ovarian cancer?

Dr. Kevin Elias:

So, first, it’s important that the diagnosis of ovarian cancer has been made with a biopsy, either a biopsy that was taken surgically or a biopsy that was taken by a radiologist. One should never receive chemotherapy based on either blood work alone, or it should not be based simply on what’s known as cytology. Sometimes patients will present with fluid in the abdomen or fluid around the lung, and the diagnosis is made only on the fluid analysis and not actually looking at the tissue itself.

There can be discrepancies sometimes between individual cells that might be present in fluid versus what you would see if you were actually looking at a slice of tissue. And so, patients should be made sure that the diagnosis is being made on an actual slide assessment of tissue. The second question that patients should ask is they should ask a little bit more about the subtype of ovarian cancer they have.

Most ovarian cancers are what are called serous cancers, S-E-R-O-U-S, like serious without the “i.” However, about a third of ovarian cancers fall under different subtypes, and those are sometimes given slightly different therapies. In fact, some types of ovarian cancer that are not serous, if they’re limited to just the ovary, chemotherapy might not even always be required for a very early non-serous type of ovary cancer. So, the subtype matters quite a bit.

Katherine Banwell:

Could you explain for our audience what biomarker testing is?

Dr. Kevin Elias:

Biomarkers are any type of additional laboratory testing, which helps guide diagnosis or therapy. So, biomarkers include special stains that we might do on the tissue itself for deciding what type of ovarian cancer it is. It would also include genetic analysis of the tissue, such as the determination whether the tumor is HR-proficient or deficient to guide therapy. There are some biomarkers that we use in order to help us determine the likelihood that somebody has ovarian cancer.

So, for instance, when we get blood tests prior to surgery, like a CA-125 test or other blood-based biomarker tests, like an OVA1 test, which involves multiple protein biomarkers, that can help us predict what the likelihood of finding cancer is at the time of surgery. But they’re not diagnostic. They’re simply a guide for helping a clinician make a decision about what they expect to find.

Katherine Banwell:

You’ve touched upon this, but how do results impact care and treatment options?

Dr. Kevin Elias:

When it comes to the type of ovarian cancer and the genetic makeup of it, it will guide what recommendations are made as far as genetic testing goes. It’ll also make decisions as far as what types of therapies would be most appropriate for a patient. Particularly as new treatments for ovarian cancer have been developed over the last couple of years, increasingly we’re seeing targeted therapy where the medication is specifically linked to a marker that’s expressed by some tumors, but not others.

And so, we would really want to know if a patient expresses an appropriate marker for targeted therapy. The HR-proficient versus deficient status is the first one of those biomarker-driven therapies that we’ve incorporated in ovarian cancer practice. But there are new biomarkers coming out, such as folate receptor expression, which are being used to guide treatment, not only in the later setting, like the recurrent setting, but increasingly in the upfront and maintenance settings with the first round of therapy.

Katherine Banwell:

What questions should patients be asking about their test results?

Dr. Kevin Elias:

They should be asking, with an initial diagnosis, whether they’re a candidate for upfront surgery or not. We do know that tumors that are amenable to primary surgical removal generally have a better prognosis than tumors that require chemotherapy to shrink them somewhat before surgery becomes an option. And so, consider having a surgical evaluation. In fact, many patients don’t see a surgeon with their initial diagnosis.

They may only see a medical oncologist. So, it’s important to have a consultation with a gynecologic oncology surgeon to determine whether or not someone’s a candidate for primary surgery. If they’re not a candidate for primary surgery, they should ask whether they’re a candidate for what’s known as HIPEC therapy, which is heated intraperitoneal chemotherapy.

That’s a special treatment which is offered after several rounds of chemotherapy, but it’s actually given in the operating room during the surgery to remove any residual disease. It’s only offered typically in specialized centers, but one should ask if HIPEC is available locally because it has been shown to help reduce the risk of cancer recurrence after completion of treatment.

Katherine Banwell:

That’s good to know. What is the difference between tumor testing versus inherited genetic testing?

Dr. Kevin Elias:

So, we think about two different genetic elements of a tumor. One part of that is the genetics that is common to every other part of the body, so the genes that we’re born with. And we sometimes refer to that as germline genetic testing or familial genetic testing.

Those would be genes like the genes BRCA1 and BRCA2 that might confer a lifelong risk of ovarian cancer, as well as other cancer types, for instance, breast cancer. There’s also the fact that every tumor cell has acquired genetic alterations that make it different from normal cells in the body. And so, we sometimes refer to this as tumor testing or somatic genetic testing, where we’re looking for genetic features that are unique to the tumor, but may not be shared by other cells in the body.

And there are therapies that could be used for mutations that are present in either the germline context or the somatic context. However, if we were talking about other cancers in the same individual or familial cancer risk, that would only apply to the germline testing scenario.

Katherine Banwell:

Now that we’ve covered testing, let’s walk through the available options for treating ovarian cancer and discuss who they might be right for.

Let’s start with surgery.

Dr. Kevin Elias:

So, the ideal surgical candidate is a patient who is otherwise relatively healthy, meaning that we think that they’ll be able to recover from surgery, typically within a few weeks of therapy, because we usually want to begin chemotherapy within a month of surgery. It should be possible to remove all sites of disease at the time of the surgery. Now, ovarian cancer, because it can involve other structures in the abdominal cavity, other than just the ovaries and the adjacent gynecologic structures, that could include surgery on the intestines, on the spleen, on the liver, in order to remove all sites of disease.

So, it’s important in choosing the correct surgeon, having a surgeon or surgical team that is comfortable with performing that type of radical surgery. So, those would be the ideal surgical candidates, patients who have disease that’s amenable to removal upfront, and the patient has to be in good functional state that it makes sense for them to pursue a potentially radical surgical option.

Katherine Banwell:

Next might be chemotherapy for some people?

Dr. Kevin Elias:

So, most patients with ovarian cancer will be getting chemotherapy, whether that’s an initial several cycles of chemotherapy to shrink the disease to make the surgery possible, or if they had a primary surgery, chemotherapy afterwards to minimize the risk of recurrence. Chemotherapy for ovarian cancer is primarily intravenous chemotherapy. We talk about medications that are gonna be given usually once every three or four weeks, depending on the regimen, and the backbone of chemotherapy for ovarian cancer is what we call platinum-based chemotherapy.

So, that means medications like carboplatin (Paraplatin) and cisplatin (Platinol) that just are platinum, like the metal-based medications, since those are really the most effective medications for treating ovarian cancer. Now, we couple it with other medicines, most commonly things like paclitaxel (Taxol), sometimes medications like doxorubicin. But platinum is really the basis for upfront ovarian cancer therapy.

Katherine Banwell:

You mentioned earlier targeted therapies. Could you go over what they are and what would be appropriate for ovarian cancer patients?

Dr. Kevin Elias:

So, targeted therapies refer to tumor therapies that specifically focus on unique genetic aspects of that tumor. So, that can be an alteration in the DNA of the tumor, it could also be a protein that’s expressed uniquely by the tumor cells. The most common one that we use currently are what are known as the PARP inhibitors. These are oral medications. They’re pills that are taken either once or twice a day after completion of chemotherapy. It’s what we call maintenance therapy.

So, the primary treatment with the surgery and chemotherapy is over, and now the patient will go on a medication they will take every day by mouth in order to minimize the chances of cancer recurrence. So, PARP inhibitors are one type of targeted therapy. The other type of targeted therapy, which is becoming increasingly common, are what are known as antibody drug conjugates. Now, these are intravenous therapies that combine a very small dose of medication with an antibody, just like the antibodies our bodies make against viruses and bacteria.

These are antibodies that have been engineered to target a protein on cancer cells. The most commonly used one right now is what’s known as the folate receptor. So, folate receptor alpha tends to be expressed more in cancer cells than in normal cells. And so, by linking a small dose of chemotherapy to an antibody against that receptor, we can target the chemotherapy specifically to the cancer cells.

Currently, those medications are used primarily for women who have already received chemotherapy, usually as a second or a third line option. However, there are clinical trials going on right now, including one which we’ve just opened at the Cleveland Clinic, where we’re using these medications now in the first line setting as an alternative to traditional chemotherapies because we think that they may be equally effective and potentially much less toxic than traditional types of chemotherapy.

Katherine Banwell:

Oh, that’s great news. What about newer targeted therapy combinations? What’s available?

Dr. Kevin Elias:

So, we are looking at other antibody drug conjugates, particularly for women who don’t express folate receptor. So, there are other protein receptors that we can develop similar type drugs for. And so, there are several of those that are in late-stage clinical trials at the moment. There’s also targeted therapy, which is using immunotherapy. So, there are ways that we can stimulate the immune system to respond to cancer cells.

In general, immunotherapy for ovarian cancer has not been quite as promising as it has been for other types of solid tumors. But that does seem to be changing. There are new immunotherapy medications, that when directed potentially in combination with targeted therapy, might produce meaningful responses. But that’s an area of active research.

Katherine Banwell:

And there’s something called intraperitoneal therapy? Am I pronouncing that correctly?

Dr. Kevin Elias:

Yes, exactly. So, there are two different contexts in which we use intraperitoneal chemotherapy. One is for patients who have had primary surgery.

So, those patients in whom the disease was felt to be amenable to complete removal at the initial surgery. There’s a very narrow group of patients. So, it has to be patients who had at least stage III disease, so disease which is involving not just the pelvic structures, but also the abdominal structures, but in whom we were able to completely remove all visible disease at the time of initial surgery. In those patients, we will sometimes leave a catheter in the abdominal cavity.

So, it’s a small, essentially IV tubing that will actually sit underneath the skin and sit next to the pelvic area. And when the patients come in for their subsequent chemotherapy, we will give part of the chemotherapy intravenously and part of the chemotherapy directly into the abdomen, essentially soaking the cancer cells directly in chemo. It is a more intensive type of chemotherapy because it does involve multiple treatments during each cycle, and it’s a much higher dose of chemo.

So, we’re really looking for patients who are typically on the younger side and generally with very, very good performance status to be considered for that type of therapy. But it is something, again, that patients should ask about if they’re a candidate for, if they’re being evaluated for primary chemotherapy and surgery. The other option as far as intraperitoneal chemotherapy would be the HIPEC I was talking about before. The heated chemotherapy is given intraperitoneally, so directly into the belly, and it’s circulated around through a special pump device during the surgery itself.

And that’s about a 90-minute treatment that’s done while the patient’s under anesthesia. So, those are the two most common types of intraperitoneal therapy. There are some other ones which are still in the investigational setting. Therapies, again, some of which we have in clinical trial, which might also be administered intraperitoneally, the idea being the shorter the distance between the delivery of the drug and the tumor itself, the higher concentration of medication we can deliver to the cancer cells.

Katherine Banwell:

We’ve talked a lot about various – excuse me – various options for treating ovarian cancer.

Are there other emerging approaches that patients should know about?

Dr. Kevin Elias:

I think important approaches for patients to know about are there are new medications which are helping us to guide interoperative decision-making. So, there’s a medication called pafolacianine (CYTALUX), which is an FDA-approved medication, which can help us to identify small tumors at the time of surgery that might not be visible to the naked eye. So, the idea there being that we know it’s important to remove all sites of disease at the time of initial surgery.

This is a medication which would be administered prior to going into the operating room, which once the surgeon feels like they’ve removed all sites of disease, they would use a special camera to try to visualize small sites of disease that maybe they didn’t appreciate the first time and then remove those during the surgery. There are some other similar investigational agents that are also under development. So, that would be another question to ask about, if a patient feels like their surgeon is a candidate for that.

As far as other novel therapies, most of them really do fall under these kinds of novel targeted therapies. What’s quite different now are the combinations of therapies. So, we’re really doing fewer and fewer studies of a single medication. It’s typically two or three medications given in combination with each other. And so, I think it’s important that patients always ask, regardless of where they are in their treatment, about whether or not they’re a candidate for a clinical trial, because we are finding more and more medications for ovarian cancer. And really, it’s a matter of sequencing. And so, at every given opportunity to understand if someone’s a candidate for something new that might be in addition to standard therapy.

Katherine Banwell:

What are the key questions patients should ask their healthcare team about their treatment options?

Dr. Kevin Elias:

The first question they should ask is, are they a candidate for surgery? Surgery, I tell my patients, should always be at least discussed as an option. The second question is, are they a candidate for a clinical trial?

Again, regardless of where they are in the treatment, there’s a good chance of trials available. And they should ask if there’s a trial, not just at the site where they’re being treated, but perhaps at other sites that might be near them. Sometimes patients are surprised to learn that there might be another center within close proximity to where they live that offers a trial, but it might not be at the primary site where they’re receiving their care.

The third question that patients should always ask is, is there an option to reduce the toxicity of their treatment? We tend to focus a lot about the efficacy of treatments and sometimes not as much on the toxicity. And what we have found is that it’s more important for a patient to be able to get through all of her therapy, rather than to have an overly toxic therapy that the patient receives an incomplete dose of.

Katherine Banwell:

You have been talking about clinical trials. Why should patients consider participating in a trial? What are the benefits for them?

Dr. Kevin Elias:

So, we’re usually trying to ask one of three questions with a clinical trial. The first question is whether a potentially new medication is effective for ovarian cancer.

And oftentimes for patients who have maybe been through several different lines of therapy, we know that patients who have gone through many lines of chemotherapy are less likely to have a good response to the next line of chemotherapy. And so, it’s a good opportunity to see if a new medication might work better for them. The second type of trial we look at is a superiority trial. We have medications that we’ve shown to be effective for ovarian cancer, and they might be better than what the patient would otherwise be getting.

And the third are trials where we’re looking at the toxicity of a drug. And I think it’s important to ask that, is the amount of medicine that I’m getting or the duration of therapy that’s being recommended to me, are we sure that that’s going to be the dose that’s going to be not only the most effective for me, but also the easiest for me to tolerate? Are there studies out there that might be looking at deescalation? And increasingly, we’re looking at whether shorter courses of therapy might be equally effective as longer courses of therapy.

Katherine Banwell:

Why is it so important for patients to participate in their care and treatment care options?

Dr. Kevin Elias:

There are several reasons for that. Oftentimes, if a patient doesn’t express interest in something like a clinical trial, a clinician might be reluctant to bring it up. They might think that the patient is simply not willing to consider that as an option. The second is that sometimes, as clinicians, we are not always the most up to date when it comes to which trials are opening or closing at any given moment. So, we may not realize that something new has come down the pike. And so, if patients don’t mention it, then their physician might not be prompted to look at it.

Katherine Banwell:

Dr. Elias, what are some of the factors that maybe prevent patients from getting the care they need?

Dr. Kevin Elias:

One of the significant risk factors for ovarian cancer is having a genetic predisposition to the disease. And one of the challenges with getting genetic testing is that most insurers will only pay for genetic testing for women who have already had cancer, or they have a family member who not only has had cancer themselves but has been diagnosed with a genetic alteration.

So, what that means is that the majority of women who have a genetic predisposition to ovarian cancer are actually unable to get that genetic testing ahead of time in a way that would allow us to perform preventative surgery to prevent the cancer being diagnosed in the first place, or to raise our suspicion that they might have cancer very early when their symptoms start to develop. So, it’s very important that women share their family health history with their providers and advocate for genetic testing if there is any cancer history whatsoever.

The second thing that delays treatment is the importance of seeing a gynecologic oncologist. There are very few gynecologic oncologists spread geographically around the country. In fact, about 90 percent of counties in the United States do not have a gynecologic oncologist. And so, it’s important to ask, whether it’s a primary care physician or a general OB-GYN, about a consultation with a gynecologic oncologist, particularly when it comes to opinions about candidacy for surgical management, as well as for selection of chemotherapy.

Katherine Banwell:

Why should patients consider getting a second opinion with another specialist?

Dr. Kevin Elias:

Sometimes when we look at a patient’s care with a fresh set of eyes, we recognize things that might not have been appreciated the first time. Sometimes there can be differences in opinion when we look at the tissue under the microscope.

Sometimes we can have differences in the radiographic interpretation. Sometimes it’s just a matter of experience. I might have had a patient with a very similar circumstance who responded to a combination of therapy that wouldn’t be inherently obvious to someone who had not seen that same scenario. Particularly whenever someone has a condition which is relatively uncommon or rare, a second opinion is certainly worth doing. But even patients with relatively common conditions, it can be worth it to have a second opinion, simply to make sure there’s consistency among different providers.

Katherine Banwell:

Dr. Elias, before we close out the program, I’d like to get your thoughts on the future of ovarian cancer care. Are you encouraged about where we’re headed?

Dr. Kevin Elias:

There’s a lot to be excited about with ovarian cancer. I think the first is on the diagnostic front, and this is really actually my primary research interest. We are getting better at developing tests which can help us predict who is most likely to develop ovarian cancer, as well as hopefully to start screening for ovarian cancer. Now, widespread screening tests, I do want to make clear, are not generally available right now.

But we’re hoping that in the near future, we’ll be able to give women better sense of who might be at risk for ovarian cancer, and prior to surgery, accurately pick out who has ovarian cancer and who doesn’t. The second is when it comes to actual ovarian cancer treatment, the medications are not only getting more effective, they’re getting more tolerable.

So, the traditional chemotherapy medications we see, or that we tend to associate with things like fatigue and nausea, not only are we better at preventing those symptoms, but the newer medications are much less likely to cause those problems. And so, we’re able to keep patients on therapy for longer with lower risks of recurrence with fewer side effects. And I do expect that to be the trend moving forward.

Katherine Banwell:

That’s great news.

Dr. Elias, thanks so much for joining us today and taking the time.

Dr. Kevin Elias:

Well, thank you so much for having me. I really enjoyed the discussion.

Katherine Banwell:

And thank you to all of our collaborators. If you’d like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready.

And don’t forget to take the survey immediately following this webinar. It will help us as we plan future programs. To learn more about ovarian cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us.