Discontinuation of poly(adenosine diphosphate-ribose) polymerase inhibitors due to adverse events in patients with recurrent ovarian cancer: A meta-analysis of three phase III trials.

Abstract

118 Background: Ovarian cancer is the fifth leading cause of cancer-related death among women. Poly adenosine diphosphate ribose polymerase (PARP) inhibitors maintenance has shown to improve survival in patients with recurrent ovarian cancer. Yet, there are notable adverse events which led to treatment discontinuation, interruption, or dose reduction. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of PARP inhibitors discontinuation due to adverse events. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2018 were queried. Phase III RCTs which employed PARP inhibitors maintenance in ovarian cancer and mentioned treatment interruption, dose reduction and treatment discontinuation due to adverse events were included. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: Three phase III RCTs with a total of 1,401 patients with recurrent ovarian cancer were eligible. The study arm used olaparib or niraparib or rucaparib while the control arm utilized placebo. The randomization ratio was 2:1 in all studies. The incidence of treatment interruption due to adverse events was 578 (61.8%) in study group versus 46 (9.8%) in control arm. The relative risk for treatment interruption was statistically significant at 5.87 (95% CI: 2.24 – 15.36, P < 0.001). The reduction in dose was reported in 496 (53.1%) in PARP inhibitors arm versus 37 (7.9%) in control group. The pooled RR for dose reduction was 7.49 (95% CI: 3.44 – 16.29, P < 0.001). The treatment discontinuation rate was 11.4% higher with PARP inhibitors than with control arm (RR - 6.84; 95% CI: 3.51 – 13.34, P < 0.001). Conclusions: Our study showed that patients on PARP inhibitors experienced some adverse events which led to significant drop outs although the definitive advantage to PARP inhibitors is still shown in the studies. Preemptive measures with proper supportive care will aide in reducing those toxicities, improve patients’ quality of life and may probably affect patients’ compliance.