Expert Discusses PARP Inhibitor Success in Ovarian Cancer

Dennis Scribner, MD

PARP inhibitors, including olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula), are revolutionizing the treatment of advanced ovarian cancer, explains Dennis Scribner, MD.

OncLive: What did you discuss in your presentation?

In an interview during the 2017 OncLive® State of the Science Summit on Ovarian Cancer, Scribner, a gynecologic oncologist at Arizona Oncology, discussed the treatment landscape for patients with recurrent ovarian cancer and how PARP inhibitors have enhanced the treatment options for this population.Scribner: My talk was designed as a backbone to give the audience a general overview of how we treat ovarian cancer in the recurrent setting. Certainly, with a gynecologic oncology patient population—since there are so many treatment options for these patients in the setting of either platinum-sensitive or platinum-resistant disease—it’s [our responsibility] as clinicians to talk to patients. We have to understand what their disease burden is and the science behind what is the best treatment for them. However, when the treatments are kind of close to equal, many treatments have many different adverse effects (AEs). Therefore [in these instances, we are also] really looking at patients’ quality of life and understanding that in a recurrent setting, these patients are not going to be cured.

Unfortunately, that is a tough thing to swallow because they go through a lot, especially in the frontline setting. When they find out they have recurred, it’s a difficult situation for them and then we focus and change our modes of therapy. There are lots of options, and [making choices] incorporates not only what they experienced before, but how long they have been in remission, what the treatment AEs are, and what their goals in their lives are. It’s about really trying to focus and pick the best therapy for them in relationship to their goals, their understanding, their deficiencies, or the AEs of not only what they have had, but what they are potentially going to have with their new drugs.

Will these PARP inhibitors potentially replace chemotherapy in the future?

We are looking ahead and understanding the PARP inhibitor concept, and this is a whole different category for us. There are people who are now living their lives and responding sometimes even better than [patients on] chemotherapy with oral agents. This is very exciting. Well, that’s a very interesting thing. I don’t think it will from a standpoint of primary therapy. When you look at drugs that we have, with the taxanes, platinum-based agents, and addition of bevacizumab (Avastin), we have a lot of patients who get into a progression-free interval in which they are in remission.

So, with advanced ovarian cancer—and unlike advanced colon or breast cancer—we go all out upfront with these big radical surgeries to reduce the tumor burdens and go all out with the most aggressive chemotherapies we have. You can talk about whether we give bevacizumab or not with that chemotherapy but, in truth, it’s hard to show a difference. We haven’t really [shown one] over many, many years of research.

In addition to those trials, what ongoing data can we expect with novel agents or combinations?

When you ask about adding PARP inhibitors to that, well, is that going to make it better? Is that going to increase more patients in remission, or lead to longer remissions? With maintenance PARP inhibitors, there is a very good question there. There are a lot of data with the SOLO and ARIEL studies that are going to come out in the next 6 months to 1 year to try and help us answer that question. I partition my mind between upfront therapy and recurrent therapy. In upfront therapy, researchers are utilizing checkpoint inhibitors; the trials with avelumab (Bavencio) are very exciting. Utilizing this idea of turning on the person’s immune system to recognize that the tumor cells are not normal cells, but abnormal cells that they need to get rid of, is very fascinating. It is a really important part of the idea of advancing that knowledge in the frontline setting.

What impact are these agents making already and how will they shift the paradigm going forward?

What are the take-home points for community oncologists who attended your lecture?

In the recurrent setting and in the platinum-sensitive category, the PARP inhibitors are really taking the limelight. We are looking at ideas of extending people’s lives and increasing progression-free intervals by 9 to 10 months. It’s even [occurring] in patients like those in the NOVA trial with niraparib, [where] patients had a benefit even if they were not somatic or germline BRCA-positive. You can actually look at that, and, with the FDA approval, everybody can get access to these drugs. It is going to be very exciting. Patients are coming into the office with discussions saying, “Tell me more about these PARP inhibitors. What does that mean?” The word is getting out, especially when you’re a patient with ovarian cancer. You’re trying to look at all of the data, trying to figure out for yourself what is best for you, and looking at oral agents that have minimal AEs—such as gastrointestinal discomfort that can be fairly managed, and anemia. You’re looking at a patient population that would automatically cling to that drug, especially with the preliminary data that we have. From a gynecologic oncology perspective, we tend to be a little bit behind in regard to trying to find molecular targets. In lung cancer and breast cancer, there are very important and known molecular targets that drugs are now related to.

So finally, with ovarian cancer, because of the PARP inhibitors we do have a molecular target: the BRCA status, whether its germline or somatic. That is a super-important part because that, fortunately, will also stimulate the community oncologists taking care of these patients to test them for BRCA status. That not only helps them with downstream treatment options or current options, but it also helps them with their family in understanding what their family’s risks are and what they can do to prevent this disease.