Comparative Efficacy and Safety of PARP Inhibitors as Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis

Abstract

This meta-analysis investigated the comparative efficacy and safety of PARP inhibitor monotherapy as maintenance treatment in platinum sensitive recurrent ovarian cancer (ROC). Electronic databases were systematically searched for relevant RCTs. The primary endpoint was PFS. The results were stratified based on three categories: BRCA mutated patients, HRD patients, and overall population. The secondary outcome were discontinuations due to adverse events and grade 3 or 4 adverse events in maintenance phase. Five eligible RCTs were included in the network meta-analysis. For patients with BRCA mutated ovarian cancer, olaparib-throughout (HR = 0.21 with 95% CrI: 0.081–0.55), rucaparib (HR = 0.23 with 95% CrI: 0.16–0.34), olaparib (HR = 0.27 with 95% CrI: 0.20–0.35), and niraparib (HR = 0.26 with 95% CrI: 0.17–0.41) were all highly effective in comparison with placebo at improving PFS. For HRD patients, both rucaparib (HR = 0.32 with 95% CrI: 0.24–0.42) and niraparib (HR = 0.38 with 95% CrI: 0.24–0.60) were all highly effective in comparison with placebo at improving PFS. For the overall population, olaparib-throughout (HR = 0.51 with 95% CrI: 0.34–0.76), rucaparib (HR = 0.37 with 95% CrI: 0.30–0.45), olaparib (HR = 0.35 with 95% CrI: 0.25–0.49), and niraparib (HR = 0.38 with 95% CrI: 0.30–0.48) were all highly effective in comparison with placebo at improving PFS. Regarding grade 3 or 4 adverse events, the incidence of grade 3 or 4 toxicity reactions to rucaparib and niraparib were significantly higher than in the olaparib group. In terms of discontinuations due to adverse events, the treatment discontinuations were not significantly different between the three drugs. In summary, all the included maintenance treatment regimens are effective regardless of BRCA mutational status, and no statistically significant differences between rucaparib, niraparib and Olaparib in terms of PFS. In terms of safety profile, the three drugs present manageable adverse events. Clinicians should consider potential adverse events related to each of these interventions in clinical practice, and the adverse events are generally manageable.

Comparison of the Efficacy and Safety of PARP Inhibitors as a Monotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis

“…The three PARPis used as monotherapy maintenance therapy for ROC were found to be highly effective in improving PFS as compared with the placebo, and there was no statistical difference between the total population and the BRCAm population, which is consistent with the results of Xu et al. ( 34 ). This provides a basis and the possibility of the expanded use of PARPis to the entire ROC patient population, as does the fact that niraparib and rucaparib can benefit PFS in people with HRD mutations, regardless of positive or negative HRD status.…”

Complete response to talazoparib in patient with pancreatic adenocarcinoma harboring somatic PALB2 mutation: A case report and literature review

“…The latest result is consistent with in vitro studies demonstrating the higher PARP-trapping potency of talazoparib compared with other PARP inhibitors (6). Results of indirect analysis of the efficiency of olaparib, niraparib, and rucaparib for the treatment of platinum-sensitive recurrent ovarian cancer also demonstrated no statistically significant differences between these agents in terms of PFS (24). Nevertheless, toxicity profiles vary significantly for approved PARP inhibitors, which may play a major role in the selection of specific treatment for PDAC patients.…”

Emerging Role of PARP Inhibitors in Metastatic Triple Negative Breast Cancer. Current Scenario and Future Perspectives

“…Recent results have demonstrated that PARP inhibitors could play an emerging role in the maintenance treatment of advanced ovarian cancer with long-term efficacy and improved PFS in patients with newly diagnosed disease experimenting CR or PR to platinum-based chemotherapy (119)(120)(121). According to these results and in the light of the emerging role of PARP inhibitors in the treatment of triple negative breast cancer, there is a solid scientific rationale for the use of these molecules as maintenance therapy even in patients with TNBC.…”