Niraparib for advanced breast cancer with germline BRCA1 and BRCA2 mutations: the EORTC 1307-BCG/BIG5-13/TESARO PR-30-50-10-C BRAVO study
Mené sur des patientes atteintes d'un cancer du sein de stade avancé et présentant des mutations constitutionnelles au niveau des gènes BRCA, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du niraparib
Purpose: To investigate the activity of niraparib in patients with germline-mutated BRCA1/2 (gBRCAm) advanced breast cancer (aBC). Patients and methods: BRAVO was a randomized, open-label phase 3 trial. Eligible patients had gBRCAm and HER2-negative aBC previously treated with {less than or equal to}2 prior lines of chemotherapy for aBC or had relapsed within 12 months of adjuvant chemotherapy, and were randomised 2:1 between niraparib and physician's choice chemotherapy (PC) (monotherapy with eribulin, capecitabine, vinorelbine, or gemcitabine). Patients with hormone-receptor positive tumours had to have received {greater than or equal to}1 line of endocrine therapy and progressed during this treatment in the metastatic setting or relapsed within one year of neo/adjuvant treatment. The primary endpoint was centrally-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), PFS by local assessment, objective response rate (ORR), and safety. Results: After the pre-planned interim analysis, recruitment was halted based on futility, noting a high degree of discordance between local and central PFS assessment in the PC arm that resulted in informative censoring. At the final analysis (median follow-up: 19.9 months), median centrally-assessed PFS was 4.1 months in the niraparib arm (n=141) versus 3.1 months in the PC arm (n=74; hazard ratio [HR] 0.96; 95% CI: 0.65-1.44; P=0.86). HRs for OS and local-PFS were 0.95 (95% CI 0.63-1.42) and 0.65 (0.46-0.93), respectively. ORR was 35% (95% CI 26-45) with niraparib and 31% (19-46) in the PC arm. Conclusion: Informative censoring in the control arm prevented accurate assessment of the trial hypothesis, although there was clear evidence of niraparib's activity in this patient population.