The approved PARP inhibitor niraparib has been beneficial for patients with recurrent ovarian cancer, but new second-line restrictions for certain patients have led physicians to be more cautious when re-challenging these patients.
Erin Crane, MD, MPH, a gynecological oncologist at the Atrium Health Levine Cancer Institute, discusses the impact of the FDA request to restrict niraparib (Zejula) in the second-line maintenance setting for patients with recurrent ovarian cancer and how, ultimately, this hasn’t vastly changed physicians’ approach.
In 2017, the FDA approved the use of niraparib, a PARP inhibitor, as a maintenance treatment for patients with recurrent epithelial fallopian tube, or primary peritoneal cancer who had a complete or partial response to platinum-based chemotherapy. This was based on early data from the phase 3 ENGOT-OV16/NOVA trial (NCT01847274).
However, a follow up of this trial showed that overall survival (OS) in the second-line setting for patients with BRCA-positive disease did not outpace the placebo. Still, the use of the PARP inhibitor has shown significantly longer progression-free survival (PFS) for patients that had a response to platinum-based chemotherapy, and in those patients with homologous recombination deficiency.
In the PRIMA trial (NCT02655016), the median PFS in the niraparib group was at 21.9 months vs 10.4 months for patients on placebo (HR, 0.43; 95% CI, 0.31-0.59; P < .001). At the 24-month interim analysis the OS rate was 84% in the treatment arm compared with 77% in the placebo group (HR, 0.70; 95% CI, 0.44-1.11). PFS in the NOVA trial also favored patients with a germline BRCA mutation in their disease with niraparib at 21.0 months vs 5.5 months in the placebo group (HR, 0.27; 95% CI, 0.17-0.41).
Crane also highlights how physicians are already adjusting the use of the PARP inhibitor depending on the patient’s sensitivity or resistance to niraparib. However, she also discusses the fine lines physicians should walk when rechallenging these patients in order to avoid adverse event outcomes like myelodysplastic syndrome.
0:08 | We talk about it and how it's going to impact our treatment, but really this study came out, and then the PRIMA trial came out…and we'd already moved a lot of the PARP inhibitors to the frontline setting. So, the question is, are you going to rechallenge these patients with PARP maintenance after they've already received PARP inhibition? And in some cases, perhaps, but for the most part, after we've used it in the primary maintenance setting, a lot of these patients who have progression will become platinum resistant as well.
0:45 | We [also] think that sensitivity to PARP inhibitors also acts as a surrogate for platinum sensitivity. So once those patients become platinum resistant, they're not candidates for PARP maintenance anyhow, so it's a little bit harder for patients that are still BRCA positive, still platinum sensitive, and may derive benefit from PARP inhibition. [However,] that's somewhere that we really need to tread carefully, and I personally have had a few patients now who have developed myelodysplastic syndrome [in this case] and it's really devastating.