Comparative efficacy, safety, and acceptability of single-agent poly (ADP-ribose) polymerase (PARP) inhibitors in BRCA-mutated HER2-negative metastatic or advanced breast cancer: a network meta-analysis

Background: Breast cancer is the most commonly diagnosed cancer and is the leading cause of cancer death in women worldwide. Both talazoparib and olaparib are approved by the US Food and Drug Administration for treating BRCA (breast cancer 1, early onset)-mutated HER2 (human epidermal growth factor receptor 2) negative metastatic or advanced breast cancer. However, the optimal choice of first-line treatment has not been determined. Objective: To compare the efficacy, safety, and acceptability of single-agent poly (ADP-ribose) polymerase (PARP) inhibitors for patients with BRCA-mutated HER2-negative metastatic or advanced breast cancer. Results: We included two trials comprising 733 participants. Compared with talazoparib, olaparib was not associated with improved PFS (HR = 1.08, 95% CrI = 0.34-3.45) or OS (HR = 1.18, 95% CrI = 0.61-2.31). Compared with talazoparib, olaparib was associated with non-significantly improved ORR (OR = 0.83, 95% CrI= 0.05-12.64). Regarding safety, olaparib had reduced risk for both grade 3-4 anemia (OR = 0.34, 95% CrI= 0.003- 34.94) and any-grade anemia (OR = 0.37, 95% CrI= 0.02-6.81) compared with talazoparib. Olaparib also showed a low risk for grade 3-4 neutropenia (OR = 0.57, 95% CrI = 0.06-5.75) compared with talazoparib. Both talazoparib and olaparib were not associated with high risk of treatment discontinuation (OR = 0.95, 95% CrI= 0.21-4.47). Regarding time to QoL deterioration, olaparib was associated with short time to clinically meaningful QoL deterioration (HR = 1.16, 95% CrI= 0.19-7.17) compared to talazoparib. Conclusion: Both talazoparib and olaparib have similar efficacy, safety, and acceptability in patients with BRCAmutated HER2-negative metastatic or advanced breast cancer. Well-designed head-to-head randomized controlled trials with large samples are suggested to determine the optimal treatment choice. Methods: We performed a systematic review and network meta-analysis. We performed a systematic search of Web of Science, Embase, PubMed, Medline, ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials, and the World Health Organization International Clinical Trials Registry Platform, and international registers for published and unpublished double-blind randomized controlled trials from database inception to July 20, 2019. The pooled estimates of hazard ratios (HR) with 95% credible intervals (CrIs) were calculated for PFS, OS, and the time to deterioration of quality of life (QoL). The pooled estimates of odds ratio (OR) with 95% CrIs were calculated for ORR, AEs, and treatment discontinuation. This study is registered with PROSPERO (CRD42019138939).

Automated summary

The study compared the efficacy and safety of talazoparib and olaparib in patients with BRCA-mutated HER2-negative metastatic or advanced breast cancer, showing similar performance in efficacy and safety, but olaparib had lower risk of anemia and neutropenia compared to talazoparib.