How to Approach to Ovarian Cancer from Community Oncology Perspective

Intro Hello again and welcome back to the Oncology Brothers Podcast. I'm Rahul Ghosain here with my brother and Co host Rohit Ghosain. Recently we've covered endometrial cancer, but today we're shifting gears to talk about another tough one, ovarian cancer. As a community oncologist, we do see ovarian cancer, so it is important to stay up to date on these recent advancements to help us navigate to current landscape and the standard of care for this disease. We're excited to have a friend, colleague and a true leader in medical education, Doctor Martina Murphy, associate professor of medicine and now also the senior associate Dean of GME at the University of Florida. Martina, welcome. Speaker 2 Thank you guys so much for having me, it's such an honor. Speaker 3 Well, thank you so much, Martina. Welcome. So to start or set the stage here, we have a patient with ovarian mass. What is your initial diagnostic workup like? These patients would sometimes come to community oncologist or rather sometimes go to Gyneong and they do undergo biopsy. It is biopsy proven ovarian cancer. What is your initial diagnostic work up looks like Particularly there are different histologies here. What scans do you go with? Is it CTCAP or PET CTNGS testing? Germline testing? What does that look like? Speaker 2 Yeah. So great question. So generally speaking, ovarian cancer like our other gynecologic cancers are actually surgically staged. So if you have a patient has a biopsy proven to have ovarian cancer, assuming that they are a surgical candidate, really the standard upfront therapy is a surgery, a primary debulking surgery by a gynecologic oncologic surgeon. And that's where you're actually going to get your official Phygo staging. Now if somebody, let's say for whatever reason is not an upfront surgical candidate, they have a lot of bulky disease or they have other medical comorbidities that maybe need to be fine-tuned before a surgery, then that's a situation where we would consider upfront chemotherapy. But generally speaking, initial sort of diagnostic staging is going to be either a biopsy followed by or a biopsy followed by a primary debulking surgery to get your full state and then that would, depending on your staging be followed by adjuvant therapy. Speaker 3 And any role of NGS or germline testing upfront at all? Role of NGS or germline testing in ovarian cancer diagnosis Yeah. So, you know, if you look at the guidelines, it is recommended that any woman with a diagnosis of ovarian cancer undergo genetic testing, germline genetic testing specifically for BRCA we also do and this we also, I personally also do NGS at the time of diagnosis. Other providers, I think, you know, may wait until later on, but I think with just all of the information and when I say later on, I mean, you know, at the time of recurrence, but I think with all of the information that could be gleaned by NGS, it's important to do it upfront. And it also just, it can be really confusing, I think with all of these different tests for different tumors, you know, when are you ordering this? When are you ordering that? For me, it makes a lot of sense logistically for our patients to just do NGS at the time of diagnosis in addition to germline genetic testing specifically for BRCA. Speaker 1 Martina, thank you so much for laying that foundation. Just reiterating what you brought up, surgery, be it in early stage or even in stage 4, cancer to debunk is very critical here when it comes to ovarian cancer. Adjuvant therapy for ovarian cancer So starting off here, a patient who's undergone surgery, how are you deciding who gets adjuvant treatment and what? Who's going to be the right partner here? Is it going to be just platinum based? Are you considering bevacizumab? What's the role of PARP in a better? Can you walk us through your thought process and adjuvant settings? Speaker 2 Yeah. So in terms of adjuvant therapy, you have it broken down nicely here in this graphic. So all stage 2 through stage 4 or patients with stage 2 through stage 4 high grade serous ovarian cancer are going to get or should get platinum based chemotherapy. I'll come back to your bevacizumab question and just a second earlier stages. So looking at the if you look at the NCCN guidelines, what they say is that stage 1A and 1B low grade, so grade 2 endometrioid tumors you can observe or you can also offer platinum based chemotherapy. Women who have higher risk disease, meaning stage 1C or clear cell high grade serous, those higher risk histologies, those are people that even though it's an early stage, stage one, they really should be given platinum based chemotherapy. And that's just because of the high risk of recurrence even in those early, early stage settings. So platinum based chemotherapy is the mainstay of of treatment for women with ovarian cancer. The bevacizumab question comes up. It really is sort of up to the individual clinician. I think there's controversy around bevacizumab because in all of the studies with Bev in the upfront setting, it does have a progression free survival benefit. But I think if you look at the studies, there's a lot of mixed data about whether or not there's an actual overall survival benefit. So if you ask like 5 oncologists, you're probably gonna get three different answers. I it's not wrong to do it in the upfront setting. I personally tend to reserve Bev for the recurrent setting. But that is if you are somebody that likes to use bevacizumab in the upfront setting, that is absolutely OK. Speaker 3 And I feel like this theme has been played out with bevacizumab in other cancers as well, particularly GBM where we have seen PFS benefit but not truly overall survival because just the anti VEGF qualities there. With this, with regards to a patient who cannot undergo surgery upfront, when relying on neoadjuvant, would you rely on again the platinum approach here and then decide on surgery in that particular scenario, any role of bevacizumab because one would have to stop that before you undergo surgery? Bevacizumab in neoadjuvant setting Yeah. So I think that's where and again it's up to the individual clinician, not wrong to use bevacizumab if you're going to be treating neoadjuvantly. But you do have to keep in mind that you have to hold bevacizumab of course, you know, for several weeks before chemotherapy. I think it gets even trickier to use it in the neoadjuvant setting just because of, you know, timing of surgery, but you absolutely can still use it and it would be the same platinum based chemotherapy regimen that you would use in an adjuvant setting. Speaker 3 And the the question of number of cycles is rather more fluid. What do you use for neoadjuvant or number in adjuvants settings? Like any particular or duration itself that you go for? Speaker 2 So what I always tell patients whenever I consent them for chemotherapy for ovarian cancer, whether or not it's, you know, adjuvant or neo adjuvant, what I always tell patients is that we're going to, you're going to get 6 to 9 cycles of chemotherapy. And the reason for that is that generally we like to do 3 cycles of treatment after surgery. So my general approach for somebody, let's say who's getting treated neo adjuvantly is we'll do 3 cycles of treatment, we'll rescan and see what kind of a response we're having. Maybe we get really lucky and it's time to go for surgery right then. And then we do 3 cycles post op. It may be that we need a little bit more chemo on board before we go to surgery. 6 cycles of chemotherapy which would then be followed by three cycles adjuvantly. Speaker 1 So Martina, a patient who's gone through surgery and gets adjuvant chemotherapy or the new adjuvant approach or more so sandwich approach because I am often giving that adjuvant chemotherapy even if they've been exposed to new adjuvant chemotherapy upfront. But then again, coming back to some maintenance therapies options available here, we have PARP and abutters. Maintenance therapies for ovarian cancer This is something that I often get confused with. Speaker 2 You and me both are cool. Speaker 1 So we have BRCA positive patients that you can use it for. You also have this option available for BRCA 1 and 2. That's wild type. Who are you using PARP inhibitors for? Speaker 2 Oh gosh, if you had asked me that a year ago, my my answer would be a little bit different than it is today. So the data is the strongest as you know, for women who have either a BRCA mutation or a BRCA like mutation, some other form of homologous recombination deficiency. So those are the women in my practice that I'm really I'm really emphasizing the benefit of PARP inhibition. You know, the data has changed a little bit and gotten a little bit confusing, I think as it's matured. Is there a benefit for PARP inhibition in women who don't have those kinds of mutations or you know, BRCA wild type don't have HRD? Yes, I there is some benefit, but you have to really weigh that benefit with the risks associated with the use of PARP inhibitors, which is are not not negligible. So I would say that in, in my clinical practice, I'm really focusing on using these drugs and women who have, like I said, a BRCA mutation, somatic or germline or some other form of homologous recombination deficiency. And then for women who, you know, want to feel like they've done every, everything known to man, you know, to try and prevent cancer recurrence, then then I talk a little bit about PARP inhibition in that case as well. But I'm really much more focused on giving it to women or offering it to women who have those those mutations that we just talked about. Speaker 1 And it's important because you brought this up, these medications are not benign just because they're oral. They give us a false sense or to our patients, a false sense of security. We use this for breast cancer, pancreatic cancer, prostate cancer here. And there are some certain side effects that we really have to be mindful about. Speaker 2 Absolutely. And I mean, I, I have, you know, taken patients who were perfectly fine from a hematologic standpoint and, you know, made them required transfusions and all kinds of things just as a result of using these medications. Of course, those are things that are manageable, but they're not benign. And like you said, I think sometimes we get, we forget that these oral medications, especially because they're taken every single day rather than every every three weeks or every four weeks, they can really have a lot of side effects that we need to think about. Speaker 3 With regards to multiple PARP inhibitors approved in this setting, any because they all have interest in side effects, any particular one that you tend to rely on one or the other at all? PARP inhibitors I tend to and this is just again my personal preference and you know personal use. I tend to rely on Elaborib when I can. Obviously you know neuroparib has the indication for BRCA wild type or or unknown status. So in that situation if you know I can't use Elaborib then I will use neuroparib. But my sort of go to again primarily because I'm really emphasizing the use of these drugs in women that have these deleterious mutations indeed is the is elaborate. Speaker 3 And sometimes, I guess whichever one provider gets used to as well. Yeah. And that's. Speaker 2 That's a lot of oncology, right? With all things being equal, we all kind of develop our personal preferences with what we're most comfortable with, what we have the most experience using and managing side effects from. So yeah, that's my approach indeed. Speaker 3 Now switching gears to relapse refractory disease where we often divide these patients into two buckets, whether it's platinum sensitive based on six months of progression versus after six months, which will be again platinum sensitive initially if it's after and if it is less than six months, then platinum resistant starting off with more of a simpler option. Relapse-refractory disease If it is beyond six months, yes, utilize platinum based therapy. However, if it's less than six months, then NGS certainly plays a role with B REFS V600E mutation her 2 positive with recent bucket approval of TDXD in this setting and also folate receptor alpha expressing tumor. How do you maneuver through all this, Martina? Speaker 2 It's very confusing. I mean, it's no, it's so nice to have options, but it also then makes it really challenging to know what to go to next. So I, the way that I interpret this. So you're right, platinum sensitive disease is, is a little bit easier, right, because you just reused platinum based chemotherapy. This is a setting in which I, I usually will add bevacizumab, so that's fairly straightforward for platinum resistant disease. My what I'm always doing in patients now at the time of diagnosis is testing for that folate receptor alpha again in anticipation of the day in which they become platinum resistant because most women with ovarian cancer will respond to platinum based chemotherapy. Unfortunately, we also know that most women with ovarian cancer will have some type of a recurrence and with time will become platinum resistant. So I'm planning ahead for the future. So I am generally knowing, you know at the outset whether or not they're, they're folate receptor positive. I will say that if they are, mirvetuximab is my first choice if it's appropriate for the patient. And we can talk a little bit about that because that's another medicine that's not without it's, it's challenges to navigate. And the reason for that for me is that that's the one that I think has the most data for overall survival benefit in platinum resistant settings. So that's my first go to. And then if there is recurrence beyond that, then that's where I use some of these other, you know, molecular markers or findings from NGS to guide my next my next move. Speaker 1 Can we take a little deeper dive here, Martina, Is there any overlap in number of patients that we see with folic receptor alpha and her two expression? Using Folic Receptor Alpha and Herceptin in Ovarian Cancer If so, would you rely on mirvetuximab or TDXD? Both are antibody drug conjugate. And again, taking a pause here for a second, when we're talking about TDXD with its bucket approval, when we're looking at all comers, pancreatic cancer, even though it's approved as a bucket approval, had an overall response rate of just 4%. But with something like ovarian cancer, it's 45%. We saw that in endometrial cancer, it's higher. It's like 5557%. Mirvetuximab has overall survival benefit. How are you making those decisions? Speaker 2 So it's a great question. And again, I think if you ask different oncologists, they'd say something different. But I tend to, like I said before, I tend to use the, when I think about ovarian cancer and I tell this to patients, I feel like I'm playing a wand game once I get to the platinum resistant space. And so I want to be strategic in the use of the agents that I'm using. And so I tend to, like I said, I tend to use Ella here first if I'm able to, and then if they are her 2 positive. And that's another thing that I can use later, you know, if they have, if they're MSI high or, you know, deficient in mismatch repair, that's another option in my back pocket that I can use. So it really just kind of comes down to sequencing and in my practice probably related to the timing of approvals. I have just started using Ala here first. If I had a patient that had both of those as options, I would use meaning the, you know, the her two positivity and the folate receptor positivity. I would personally probably use the Ala here first, but it certainly wouldn't be wrong to do it the other way around. Speaker 3 And given the recent sorry, I'll go. Do you see response when you sequence ADCs after another? For it talking about sequencing one thing, when it comes to ADC, we've seen this more so in breast cancer. If you're exposed to one ADC there we're talking about tropotosacitisumab and then exposing to another ADCTDXD. We continue to see that there are some unique differences. Do you see that there's still response when you're sequencing one ADC after another here, Martina? Speaker 2 You know, it's interesting because this is really the 1st the ADC and the ovarian cancer space. So I don't know that we have that information yet. So I can't effectively answer your question, but I would imagine that, well, I know that there's a lot that we have to learn in this space using this ADC, and I know that it won't be the last. Speaker 3 And given the recent approval, we will be using more of mirvetuximab in our community settings. Any important clinical pearls for us to actually and especially with the dose reduction or managing some of these side effects? Speaker 2 Yeah. So I think, you know, for all of our ADC's, certainly Ella here is no different. I think one of the things that really gets people's attention is the concern over the ocular toxicities. I know that's something that's very scary to some of my colleagues, certainly is very scary to patients when you start to consent them for this drug. It is interesting because people are willing to, at least in my experience, patients are willing to accept a lot of side effects. But if you start to talk about, you know, loss of sight, that is very scary understanding. So a couple of pearls. I think it's really important to know and to talk to patients about the fact that these, the ocular toxicity and the other toxicities are very manageable. So, you know, I think if you look at the study, there were very, very few patients who actually experienced ocular toxicity that was not reversible. The number wasn't 0. But in general, this is a very, very manageable toxicity. So that is something that can really can reassure patients. And that's true of the other side effects that we see with Ella here. I think one of the tricks with Ella here is that you do have to have a partner in your area, in your community or your center who can do slit lamp exams. We can do a lot of things as oncologists. Speaker 1 But I can. Speaker 2 Tell you guys, I have not learned how to do slit lamp exams. And so it is actually an important part of of the label that patients are getting a slit lamp exam. I think it's every other cycle they have to have slit lamp examination done just to make sure that you know, we're we're effectively managing any ocular toxicities that come up. So that can be a challenge. And I think it it is helpful to be able to identify somebody in your community or in your in your practice that can kind of be your go to person. But I will tell you that has been a challenge for me. I have, I have made the decision to not put put a few patients on LA here because I wasn't sure that they were going to be able to effectively follow up with an outpatient optometrist or ophthalmologist. And that's another important point. It doesn't have to be an ophthalmologist. It can be an optometrist. Sometimes there's access issues with one versus the other. Speaker 1 When we're talking about toxicity, I think it's important. We've touched some for PARP inhibitor. Is mirvetuximab even for trustism? Abdur XT can things like nausea, alopecia, fatigue, of course, pneumonitis. We've touched, Martina, you brought up immunotherapy, immune related side effects when we're using that, those are the things, it's not just the approval. As a community oncologist, I really need to get comfortable with these drugs and how to manage some of the side effects that come along. Martina, just before we close, we talked about PARP inhibitors. If you've not used this upfront and wild type, are you planning to use that in platinum resistance space? Speaker 2 I generally, it's, I sometimes will, but generally speaking again, I have, I have, I with time I have started to steer away from carb inhibitors outside of women who have one of the mutation, the Braca or other form of HRD that we know really shows the big magnitude of benefit, but it certainly is an option. Speaker 3 Well, Doctor Murphy, thank you so much for taking your time and reiterating the current standard care for ovarian cancer for our listeners. Let us go or a quick. Speaker 1 Recap In today's discussion with Doctor Martina Murphy, we had a chance to focus on the current landscape of ovarian cancer. The surgery remains a key cornerstone in management of this disease, but genetic testing and NGS are also critical in guiding our treatment in adjuvant settings. Platinum chemotherapy remains the standard of care at this time, then we. Speaker 3 Also had a chance to touch on the importance of testing for her two IHC to explore trastuzumab duresticaine as a treatment option or folic receptor alpha to ensure mirvateximab as a potential option in recurrent and metastatic diseases essential. Thank you for tuning in. Please make sure to check out our other discussions around the practice, changing data and the current standard of care treatment options. We are the oncology brothers.