Molecular Testing and Ovarian Cancer

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Chad A. Hamilton, MD, and Robert W. Holloway, MD, discuss challenges clinicians face in treating ovarian cancer and review the current state of biomarker testing.

Chad A. Hamilton, MD: Welcome to this OncLive® My Treatment Approach program on ovarian cancer. I’m Chad Hamilton, a gynecologic oncologist and an associate research director at the Ochsner Cancer Institute in New Orleans [Louisiana]. I’m pleased to discuss approaches to the management of patients with ovarian cancer along with my colleague Dr Robert Holloway, who is the medical director of and a gynecologic oncologist at AdventHealth Cancer Institute in Orlando, Florida. Let’s get started. We’ll have a little discussion about context first, Dr Holloway, and then we’ll talk about some cases and how we would manage those. From a broad landscape approach, what do you see as some of the greatest challenges in treating patients with ovarian cancer? Specifically touch on frontline ovarian cancer. What are the greatest challenges there? We’ll get into more detail in a bit.

Robert W. Holloway, MD: It’s well known that our greatest challenge with ovarian cancer is that most of our patients still present with advanced-stage disease, which requires multimodal therapy to get the disease under control. We’ve made great advances in the past 30 years with new drug therapies and new supportive therapies for getting patients into clinical remission, but what hasn’t changed much is that the vast majority of our patients relapse with symptomatic disease at some point in their lifetime, at least 75% to 80%. Of course, we’ve had recent advances in maintenance therapies to maintain or prolong that disease-free survival, but at the end of the day, most of our patients relapse and succumb to their disease, and I view that as the single biggest challenge to improving overall survival. We’ve made some bumps in that during my tenure as a GI [gastrointestinal] oncologist over a few decades, but we’re not hitting home runs yet. We’re getting on base, though.

Chad A. Hamilton, MD: Yes, I agree. Absolutely. Thinking a little about first-line treatment for ovarian cancer, because that’s where our focus is today, the challenge for me is that it almost comes as a series of choices that we have to make in the front-line setting. Maybe the first is [whether] this is a patient for primary debulking surgery or if this is a neoadjuvant chemotherapy patient. Once we make those decisions—do we layer in bevacizumab with that treatment? Which patients are appropriate for bevacizumab?—and then continue it as maintenance, how do other biomarkers help us determine treatment in the front line and of course maintenance therapy. I’m happy it’s gotten a lot more complicated and confusing; frontline therapy wasn’t that long ago. There was carbo-Taxol [carboplatin, paclitaxel] and maybe a couple of derivations of that, but it’s evolved a lot and changed in the past 5 years.

To touch on that biomarker question a little more, and the landscape of that, we’ve seen a dramatic evolution. We were initially testing folks guideline based for germline BRCA mutations. That’s evolved as we’ve learned more about this homologous recombination landscape and all these factors playing into the machinery of DNA editing and how we test for that. Can we test for that? Whom should we test for those things? To be honest, I’ve done it a number of ways, and even in the past year, how I layer those things has changed.

The first challenge is to discuss biomarker testing with patients. It’s hard enough in a short 15-minute appointment to teach them what germline testing is vs somatic testing, and they’re both very important parts of ovarian cancer treatment when deciding on first-line treatment. I introduce that into the discussion at 1 of the first visits after the patient has started to digest their disease and what’s going on. In the context that we need to start treatment, these are some things that may help us with decisions now and down the line. I’ve done it a couple of different ways. I’ve done germline testing first and the reflex into somatic testing.

The question of HRD [homologous recombination deficiency] testing has come into play a little more. What type of testing should we be doing for homologous recombination? Are they all the same? Are they all different? I’m testing for both germline BRCA mutations and homologous recombination. I’m currently using the Myriad [Genetics] platform, and I’m doing those not in sequence but at the same time if possible, which is a bit of a challenge when neoadjuvant chemotherapy comes into play [because we have to] get the best specimen for those tests. That’s what I’ve evolved into. It’s an ongoing process, but I try to do both germline and somatic testing. My preferred in this up-front testing right now is the HRD platform, which uses a combination of factors to come up with a risk for patients.

Transcript edited for clarity.