Classification of Ovarian Cancers

Transcript:Bradley J. Monk, MD: Hello, and thank you for joining this OncLive Peer Exchange® titled “Expert Views on Therapy for Ovarian, Fallopian Tube, and Peritoneal Cancers.” Ovarian cancers remain a very challenging disease. Most are diagnosed with late-stage disease, most recur, and patients are receiving more and more treatments—treatments that are complex. But fortunately, new treatments are available. It’s my pleasure to remind you that we have had 3 new FDA approvals for targeted therapies in the last 2 years, and I anticipate within the next year, we’ll have 3 more. So, this is an exciting time for novel therapies. Our armamentarium is growing and our paradigms are changing.

It’s my honor today to be joined by my friends and colleagues from all over the country. I’m Brad Monk. I’m a gynecologic oncologist and professor at the University of Arizona and Creighton University School of Medicine at St. Joseph’s Hospital (regional campus) in Phoenix, Arizona. Joined here to my left is Dr. Robert Coleman, vice chairman and director of research from MD Anderson Cancer Center. Welcome, Rob. I’m also here with Dr. Tom Herzog, associate cancer center director at the University of Cincinnati, also a gynecologic oncologist and professor. Welcome, Tom. Then we have Dr. Kathleen Moore. Dr. Moore is from the Stephenson Cancer Center at the University of Oklahoma, also a gynecologic oncologist and a phase I expert. I love it. Thank you and welcome. And then we have Dr. Angeles Alvarez Secord, professor in the Division of Gynecologic Oncology at Duke University School of Medicine in Durham, North Carolina. Angeles, welcome.

Angeles Alvarez Secord, MD: Thank you for having me.

Bradley J. Monk, MD: You’re welcome. We have a number of segments today, and I couldn’t be happier. As I said, the paradigms are changing, the therapies are more diverse. We have novel approvals that have just occurred, 1 just recently, and then hopefully 3 that are probably around the corner. I’d like to talk about the different subtypes of epithelial ovarian cancer. So, the title of our program is “Ovarian Cancer, Fallopian Tube, and Peritoneal Cancers.” It’s really 1 entity, but Rob, we know a lot about the different subtypes. Even though they’re different organs of origin, tell us about the different subtypes of epithelial ovarian cancer.

Robert L. Coleman, MD: That’s a good lead-in because I think we’ve all known for many years that there are morphological differences looking at these cells under the microscope. The histologies can vary from the most common type—the hybrid serous tumor—through a variant we think is really a different disease. They are called low-grade serous, clear-cell, endometrioid, and mucinous, and they are distinctly different from the way they look. But it’s interesting because the molecular information that we’ve now subsequently learned from the TCGA and multiple other data sets delving into these histiotypes even more, we’re finding out that they actually can segregate even within cells that all look the same. And I think that’s where a lot of what we’re going to talk about stems from. So, we have these new launch points that identify these subclassifications, where therapies might be developed into a better outcome or better expectation.

Bradley J. Monk, MD: About 85% of our cancers are these high-grade serous cancers; 15% are sometimes high-grade endometrioid and those are pretty homogenous. But then, low-grade serous, clear-cell, and mucinous cancers really are a different entity. So, Katie, do you treat those low-grade serous, mucinous, and clear-cell cancers differently? You just heard Rob say they’re not the same.

Kathleen N. Moore, MD: Right.

Bradley J. Monk, MD: So, you treat them differently, right?

Kathleen N. Moore, MD: We know they’re not the same. Currently, the standard of care is still to choose the same chemotherapy backbone, although there are clinical trials in development. We’ve completed some in mucinous, which, unfortunately, didn’t lead to a different standard of care, but we’re still looking. For low-grade, there’s discussion of using different agents in the frontline, actually moving away from platinum- and taxane-based frontline therapy and using more targeted therapy because we know that chemotherapy doesn’t work. We’re too nervous not to use it. We’re finally getting brave enough to run a clinical trial that’s going to test whether or not those patients need chemotherapy at all.

Bradley J. Monk, MD: So, I think what I heard is you don’t want to treat them the same, but you do anyway. Is that what you said?

Kathleen N. Moore, MD: I think that’s an accurate statement.

Bradley J. Monk, MD: Angeles, how does that change the prognosis?

Angeles Alvarez Secord, MD: The prognosis between these different subtypes is certainly variable, so high-grade serous patients tend to have the worst prognosis compared to those with low-grade serous cancers. Low-grade serous cancers tend to act in a more indolent fashion. Patients with early stage mucinous, clear-cell tumors, and low-grade endometrioid cancers tend to do better. Patients with clear-cell or mucinous advanced-stage disease tend to do much worse.

But I want to drill down even farther into the high-grade serous tumors. Even within that entity, as Rob was mentioning, there are different classifications. One of the big ones seems to be whether or not that tumor harbors a homologous recombination defect, and the most common HRD (homologous recombination deficiency) tumors are those with germline or somatic BRCA mutations. So, we can drill down even to that group. You were asking about prognosis. In that group of patients that have high-grade serous ovarian cancers and have mutations in these genes, their prognosis is much better compared to women who have non-BRCA—mutated tumors.

Transcript Edited for Clarity