Expert Discusses PARP Inhibitor Explosion in Treatment Landscape of Ovarian Cancer

Erin K. Crane, MPH, MD

Erin K. Crane, MPH, MD

The use of immunotherapy agents for the treatment of gynecologic cancers is currently a hot topic in the field, with various clinical trials ongoing. The success of PARP inhibitors has also exploded over the past year, translating to improvements in progression-free survival and quality of life for some patients, says Erin K. Crane, MPH, MD.

One of the biggest challenges, however, is that women and minorities are vastly underrepresented in clinical trials. Loss of funding due to government funding cuts has also made this a difficult challenge to overcome, but Crane says part of the issue is already being addressed by working with pharmaceutical industries to open more clinical trials.

In an interview with Targeted Oncology, Erin K. Crane, MPH, MD, a gynecologic oncologist at Levine Cancer Institute, highlighted ongoing research in ovarian cancer, as well as the unmet needs that still exist for these patients.

TARGETED ONCOLOGY:What is the current role of PARP inhibitors in ovarian cancer?

Crane:PARP inhibitors have really come up over the last few years in ovarian cancer. In December 2014, olaparib (Lynparza) was approved for use in patients with germline BRCA mutations who have had 3 or more prior treatments. Then over the past year, it's really exploded. Drugs like rucaparib (Rubraca), olaparib, and niraparib (Zejula), have come to the forefront in patients with recurrent disease. There have been some trials that have been done, not just looking at patients with germline BRCA mutations, but all comers with platinum-sensitive disease. As a result, there have been FDA approvals. What that translates to for patients is, in some cases, almost a year improvement in progression-free survival with a really good quality of life on those medications. 

TARGETED ONCOLOGY:Are PARP inhibitors being looked at in combinations?

Crane:Yes, absolutely. If you go on the National Institutes of Health (NIH) website, there are at least 30 trials looking at combinations of PARP inhibitors. One of the interesting questions we're asking is whether or not they can be used as maintenance in the frontline setting in combination with other chemotherapies, as well as in the recurrent setting in combination with both targeted drugs and with some of the chemotherapy regimens that we use.

TARGETED ONCOLOGY:Are toxicities a concern with combinations?

Crane:As is true with any cytotoxic chemotherapy, when you combine drugs, there tends to be a higher toxicity profile. I think we're learning a lot more from the trials. Primarily, we have to be careful with bone marrow suppression. The nausea tends to be a little bit worse, but we have good medications to help with that, and if you can get patients to stick with it after the first couple of weeks, that tends to improve.

TARGETED ONCOLOGY:What is on the horizon with immunotherapy for the treatment of gynecologic cancers?

Crane:This is also a very hot topic. For cervical cancers, which are HPV-related and very immunogenic, there have been a lot of exciting developments. We actually have a phase I trial open at our institution, and we've had some patients with recurrent cervical cancer who have had complete responses, which is almost unheard of. It's a really difficult patient population to treat, so we are very excited about that. In patients with endometrial cancer who have microsatellite instability, there has been some promising data, and then also in clear cell ovarian cancers. Those patients traditionally have had relatively chemotherapy-resistant disease and are having some really good responses to immunotherapy. 

TARGETED ONCOLOGY:In your opinion, what is the biggest unmet need for these patients?

Crane:As you're probably aware, women have historically been underrepresented in clinical trials, as have minorities. We’ve have also seen significantly decreased funding for our trials over the past several years. If you look at enrollment for gynecologic malignancies in phase III trials, it's gone down by 90%. We're so dependent on those trials to come up with new treatments for our patients that without them, our treatments are really stagnant.

It's not all negative, though. We are working now with more pharmaceutical industries to open more trials. I think we're starting to gain some momentum, but we need to start getting those women enrolled in phase I, phase II, and phase III trials, as well as some of the minority patients who are disproportionally not enrolled on those trials. It's an unmet need.

TARGETED ONCOLOGY:In the future of this treatment landscape, where do you see it headed in the next 5-10 years?

Crane:I think immunotherapy is a really exciting field. Certainly, you hear the terms “personalized medicine” and “precision medicine.” We're becoming more informed about tumors, what they're susceptible to, targeted treatments, and how to take cancers that maybe are not immunogenic and make them more attractive to immunotherapy and immune agents. That will be something we will look forward to in the future.

TARGETED ONCOLOGY:What studies are currently ongoing at your institution?

Crane:We have some really exciting phase I, phase II, and phase III trials open at our institution. My personal interest is in high-risk endometrial cancers, so they compromise a much smaller proportion of endometrial cancers, but a much larger proportion of endometrial cancer-related deaths. For whatever reason, African American women tend to be more prone to uterine-serous carcinomas, and carcinosarcomas, and have worse outcomes. My interest is in looking at the molecular profiles of those tumors and trying to figure out why there is that difference and if there's a treatment we can aim towards those patients.