Treatment Advances in Ovarian Cancer and Other Gynecologic Malignancies

December 1, 2016 7:06 pm

The following article is provided by The Clearity Foundation to support women with ovarian cancer and their families. Learn more about The Clearity Foundation and the services we provide directly to women as they make treatment decisions and navigate emotional impacts of their diagnosis.

Treatment Continues to Advance in Ovarian Cancer and Other Gynecologic Malignancies

There has been major progress in treating gynecologic malignancies in recent years, especially for ovarian cancer, says Douglas A. Levine, M.D., a member of The Clearity Foundation’s Scientific Advisory Board.

For example, PARP inhibition has gained impressive traction as a therapeutic option for patients with ovarian cancer. In 2014, Lynparza (olaparib) was approved for the treatment of patients with BRCA-positive advanced ovarian cancer following treatment with three or more prior lines of chemotherapy. Ongoing phase 3 trials are examining the agent as maintenance therapy or an alternative to chemotherapy in women with recurrent disease.

Rucaparib was granted a priority review by the FDA in August 2016 for patients with BRCA-positive advanced ovarian cancer who have received two or more prior lines of chemotherapy. A final decision is expected by Feb. 23, 2017.

And in November 2016, a new drug application to the FDA was completed for niraparib as a maintenance treatment for women with recurrent platinum-sensitive ovarian, fallopian tube or primary peritoneal cancer.

In an interview with CURE at the recent 2016 Chemotherapy Foundation Symposium, Levine, professor, Department of Obstetrics and Gynecology, director, Division of Gynecologic Oncology, NYU Langone Medical Center, discussed these agents and other advances toward precision medicine in the treatment of patients with gynecologic malignances.

Can you provide an overview of your presentation?

When it comes to precision medicine, there are many important aspects that will affect the way we take care of cancer patients. One part of my talk focused on diagnostic dilemmas, because treating the cancer patient really starts with a correct diagnosis, and we partner with our pathologists very closely. The gynecologic pathologist is a very important part of the gynecologic oncology team, and it’s important to have a correct diagnosis to treat somebody. Precision medicine can help us make sure we’re treating the right patient with the right tumor when we use novel molecular diagnostics with traditional pathology. Traditional pathology gets you to the right place, and molecular pathology can then hone in on the diagnosis.

What are some of the immediate next steps to take?

As of now, we have a very exciting class of drugs called PARP inhibitors, and they’re very effective in women who have tumors with a BRCA mutation, but the exciting part now is to figure out what other tumors are going to respond to PARP inhibitors, and how we can combine PARP inhibitors with other agents to make them more broadly available to the oncology community.

What potential combination regimens are emerging with PARP inhibitors?

Combining PARP inhibitors with chemotherapy agents has been a little bit difficult, but we do have an ongoing trial, and we’ll see what that shows. I think in the recurrent setting is where they’re really going to be the most effective, and combining them with immunotherapy, with angiogenic therapy, and with other agents that we can’t even think about today — you know, cell cycle inhibitors, where we can really harness that potential — it’ll be very exciting.

What impact do you expect agents like rucaparib and niraparab to have on the treatment landscape?

I think there will be many PARP inhibitors to choose from over time, and some of the big questions are where to give them and how to give them. Whether to give them in the maintenance setting or the treatment setting, whether to use them early or late—these are very good questions. Personally, I prefer to use them early on in the treatment cycle. As far as using them in the maintenance setting or the actual treatment setting, I think that is something we’ll learn about as time goes on.

What can you say in terms of the tolerability of these agents?

There are many concerns about tolerability and toxicity. Even though these are oral agents, they do have substantial toxicities, including fatigue, anemia, a need for blood transfusions, and other sorts of concerns. That’s why some people think that the maintenance setting may not be the best place, and the treatment setting may be more appropriate. So we have to carefully balance the toxicity with the benefit, which is true of all of our new cancer treatments.

What are some of the main challenges in ovarian cancer that you hope to tackle?

I hope we’ll be able to stratify patients better. We’ve certainly come a long way with those patients who have BRCA mutations. We’re making progress in getting every patient with ovarian cancer tested for BRCA germline mutations.

We have a very aggressive group that has cyclin E1 amplifications, and there’s exciting laboratory research going on, and I look forward to translating that into the clinic. Then we have this group that some of us call “the others.” They don’t have the BRCA mutation, they don’t have a homologous recombination deficit, and they don’t have a cyclin E amplification. They have something else. How can we develop therapies that will target that group? I think that’s what we’ll see in the future.

What would you like the oncology community to take away from all of this?

I’d like people to realize that we are making progress. Patients with ovarian cancer are living longer and better. We have great opportunities for prevention. We can make a dramatic impact in the mortality of ovarian cancer simply from prevention, and we can do that today. It’s also important to understand how PARP inhibitors and other agents work, and there will be a lot of new therapies in clinical trials and new approvals in the coming years.

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