Considering PARP Inhibitor Maintenance in Ovarian Cancer

Shared insight on the selection of PARP inhibitors for maintenance therapy in ovarian cancer with deference to patient and disease factors.


Leslie M. Randall, MD: For PARP inhibitors, we have 3 medications that are currently FDA [Food and Drug Administration] approved and they’re approved in a variety of settings. If you’ve had a little trouble following exactly where we’re using PARP inhibitors, you’re not alone. This has evolved very rapidly from the very first approval of olaparib [Lynparza] in 2014 for BRCA-mutated treatment. We’ve really evolved most of our PARP inhibitor treatment to the maintenance setting. It was approved in [the] platinum-sensitive maintenance setting a few years ago, and 3 drugs are approved in that setting—olaparib, niraparib [Zejula], and rucaparib [Rubraca]. It appears that for the most part, they have fairly equal efficacy and similar toxicity. There are some differences in how they’re dosed and their metabolism that may play a role in how one would choose among the 3. But in the frontline, we have olaparib and niraparib currently with rucaparib still in the investigational setting in the frontline. The way it looks with PARP inhibitors, the earlier you give them is probably the better they work. Most of us who have a lot of experience with PARP inhibitor maintenance have transitioned to using this in the frontline for all of our patients. Currently, olaparib is approved as a single agent for BRCA-mutated cancers and HRD [homologous recombination deficiency] tumors when it’s given in combination with bevacizumab [Avastin]. Niraparib on the other hand is approved for all biomarker groups and all tumor types. Now, some argue that it has more efficacy in the biomarker positive groups and that’s true. However, it does have efficacy in patients who are HR [homologous recombination] proficient. And interestingly, in this frontline, this is probably the HR proficient [patient’s] best chance to benefit from a PARP inhibitor. A good portion of those patients will become platinum-resistant, and the PARP inhibitors are currently not approved in the platinum resistance setting except for patients who have BRCA mutations. The hope would be that patients would receive it earlier rather than waiting for that to be given as a therapy. Frontline maintenance is really the target time for PARP inhibitor administration and if they miss it in the frontline then in their first platinum-sensitive recurrence if they hopefully make it to that platinum-sensitive mark.

The PRIMA trial established niraparib as a frontline treatment option, maintenance option for patients. It was a really interesting trial and exciting trial because at the time that the PRIMA trial was performed, we only had PARP inhibitors available for our BRCA mutated patients. We had seen remarkable efficacy with PARP in the BRCA negative population; 70% reduction in the risk of progression or death in the SOLO-1 trial, but we had not yet seen the efficacy in a non-BRCA mutated group. BRCA mutated patients were eligible for this study and enrolled high-grade serous and endometrioid types that were stage III or IV and were deemed to be high risk for recurrence. And that could be patients with neoadjuvant chemotherapy and suboptimal developing patients. Basically, most of the patients that we see, so this is a very common population that was enrolled into PRIMA. In PRIMA, they were enrolled after their frontline surgery and chemotherapy. They had to have been in a complete or partial response, and if they were, they could be enrolled and randomized 2:1 to niraparib vs placebo in the maintenance phase. This trial was really interesting because we already had niraparib approved by the NOVA trial that was performed in the platinum-sensitive setting. Platinum sensitivity is a marker for PARP sensitivity. In the frontline setting, you don’t know yet if patients are going to be platinum-sensitive or not. I assumed that we would probably not see as good of efficacy in the frontline with niraparib and this all-commerce population and I was wrong. In the BRCA mutated patients that were enrolled in the trial, niraparib showed similar efficacy to that which was seen with the olaparib in SOLO-1. For the HRD patients, this hazard ratio was 0.43, so that was considerable efficacy in this all-comers population. Now the HR proficient patient population had less efficacy but it was a smaller group and it’s really difficult to draw conclusions from their singular outcome. The overall conclusion of the study was that the full population derives significant benefit from niraparib. I consider niraparib an option for all of my patients that have stage III or IV endometrioid high-grade serous cancer and/or have responded as a complete or partial response to their frontline chemotherapy. So that is most of my patients actually. That is most of my ovarian cancer patients and I consider them candidates because of this benefit.

Transcript edited for clarity.

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