Review Offers First Head-to-Head Look at PARP Inhibitors for Ovarian Cancer

For the first time, researchers have compared the 3 approved poly-ADP ribose polymerase (PARP) inhibitors for platinum-sensitive ovarian cancer in a head-to-head analysis, concluding that there are no significant differences between the treatments when it comes to survival. They did, however, find that safety varied between the treatments.

Drawing on data from 6 randomized controlled trials accounting for over 2200 patients, the researchers compared the demonstrated efficacy and safety of olaparib, rucaparib, and niraparib.

Five of these studies offered data on progression-free survival (PFS) among patients, throughout which all 3 treatments resulted in statistically significant improved PFS compared with placebo. Compared with placebo, the hazard ratio (HR) for niraparib was 0.6; for rucaparib, 0.7; and for olaparib, 0.72.

Specifically looking at PFS among patients with BRCA mutations, data from 4 studies showed that niraparib (HR, 0.69) and olaparib (HR, 0.76) both showed a statistically significant advantage over placebo, while rucaparib did not (HR, 0.79). Meanwhile, among the 3 trials that included wild-type BRCA patients, all 3 treatments statistically improved PFS over placebo.

These findings were consistent across the 2 trials that assessed the overall survival advantage of olaparib and niraparib against placebo.

However, differences among the PARP inhibitors became evident when the researchers parsed through safety data, finding that statistically significant differences were observed. While all 3 treatments raised the risk of anemia (any grade and grade 3-4), as well as decreased appetite, dizziness, dyspnea, fatigue, nausea, neutropenia, and vomiting (any grade), niraparib carried a significant higher risk of thrombocytopenia than the other 2 PARP inhibitors.

“It is important to note that both the Nova trial and the Prima trial initiated niraparib at a dose of 300 mg. However, the Nova trial protocol and the treatment recommendations have since been amended due to data from a retrospective study that showed that a niraparib dose of 200 mg was effective and caused fewer AEs for patients with either a baseline body weight of less than 77 kg, a platelet count of less than 150,000 per cubic millimeter, or both,” explained the researchers.

Constipation was heightened among patients treated with olaparib, and rucaparib was associated with more headaches.

According to the researchers, these differences could be credited to their selectivity; they cite a recent study in which the data showed niraparib was more selective towards PARP1 and PARP2 while the olaparib and rucaparib were more potent inhibitors of PARP1 but less selective. Other studies have suggested that rucaparib and olaparib have different in vitro affinity profiles.

Reference

Stemmer A, Shafran I, Stemmer S, Tsoref D. Comparison of poly (ADP-ribose) polymerase inhibitors (PARPis) as maintenance therapy for platinum-sensitive ovaraian cancer: systematic review and network meta-analysis. Cancers. 2020;12(10):3026.