Taking Action to Individualize Ovarian Cancer Care: Excitement Surrounding PARP Inhibition

In this fourth episode of OncChats: Taking Action to Individualize Ovarian Cancer Care, John Nakayama, MD, of the Division of Gynecologic Oncology, Allegheny Health Network, and assistant professor of OBGYN at Drexel University, and Christopher B. Morse, MD, gynecologic oncologist, Allegheny Health Network, discuss key developments made with PARP inhibitors in the ovarian cancer treatment paradigm.

Nakayama: Dr Morris, can you tell me a little bit about why there is so much excitement around PARP inhibitors [in ovarian cancer]? What do [these agents] actually bring to the patient?

Morse: A lot of what we are getting so excited about are data that have come out of several large randomized trials, all of which had been published in the New England Journal of Medicine. [These trials have all] looked at the impact of adding [a] PARP inhibitor to the frontline setting.

The [phase 3] study that came out in 2018, was called SOLO-1 [NCT01844986], and [this] looked at just patients [with the BRCA1/2] mutation who were given olaparib [Lynparza] after completion of initial carboplatin/paclitaxel chemotherapy. [Results] showed a very, very striking improvement in median progression-free survival [PFS]. The most recent updated data showed a PFS of 56 months vs almost 14 months in those who had a mutation and those who did not.

Other PARP inhibitors, such as niraparib [Zejula], have also been studied in this setting. It is important to know about the [phase 3] PRIMA study [NCT02655016], which came out in 2019. This [study] looked at patients who either had a mutation and were found to be homologous recombination deficient [(HRD) or] those who were homologous recombination proficient. In this study, we saw a similar increase in the median PFS [with the PARP inhibitor, at] 21.9 months vs 10.4 months. [These findings were] not quite as striking as the SOLO-1 data, but still significant. Even in all comers, meaning all patients who are enrolled to the study, we also saw an improvement in the median PFS [with the PARP inhibitor] that was [found to be] significant.

[Another] exciting thing has come out and helps us [sequence] therapy in the frontline setting. What if you have a patient who, for whatever reason, you have them on bevacizumab [Avastin] in the frontline setting, and then you find out that they have a mutation? [Should we] be adding a PARP [to the mix] for those patients? [The phase 3] PAOLA-1 [study (NCT02477644)] showed that the patients, especially those who are HRD, or mutation carriers that are on bevacizumab maintenance with olaparib maintenance, have a similar fairly impressive improvement in their PFS of 37 months vs 17 months.

For us, as gynecologic oncologists, all these data are really, really exciting. [They are] pushing the envelope further for our patients, improving their PFS. [PARP inhibitors are] generally an [approach] that is well tolerated. It really is an exciting time in gynecologic oncology.

Nakayama: You are 100% right. We eagerly await the overall survival data at this time. Some of the points that you touched on are really important. [I will note] that SOLO-1 [included patients with] BRCA only. As Dr Morris mentioned, the PRIMA trial had [patients with] both HRD and [BRCA] in this, so not exactly the same population. That is part of the reason why their PFS is a little bit lower. I think the other thing that is really interesting about this is in POALA-1, there was not a PARP-only arm; it was bevacizumab vs bevacizumab plus olaparib. What is very interesting is even when you have a known active agent, and you add a PARP inhibitor on top of it, you still see some additional benefit.

Check back next Wednesday to view the next segment in this series.