BROCADE3

BROCADE3 (NCT02163694) randomised 513 patients (509 in the intention-to-treat population with a centrally confirmed germline BRCA mutation; 337 veliparib, 172 placebo) between July 2014 and January 2018 to carboplatin AUC 6 on day 1 and paclitaxel 80 mg/m2 on days 1, 8 and 15 of 21 with veliparib 120 mg or placebo twice daily on days minus 2 to 5, continued at an intensified dose as monotherapy if chemotherapy stopped before progression; the control group could cross over to veliparib on progression. Median progression-free survival was 14.5 versus 12.6 months (hazard ratio 0.71, 95 percent confidence interval 0.57 to 0.88, p 0.0016). Final overall survival (European Journal of Cancer 2024) was 32.4 versus 28.2 months (hazard ratio 0.916, 0.736 to 1.140, p 0.434). Grade 3 or worse neutropenia occurred in 81 versus 84 percent, anaemia 42 versus 40 percent and thrombocytopenia 40 versus 28 percent. The trial matters for triple-negative disease because roughly half of germline BRCA breast cancers are triple-negative and because it is the only phase 3 of a PARP inhibitor given with, rather than instead of, chemotherapy: the progression-free survival gain did not become a survival gain, and the 28-month median survival of the carboplatin and paclitaxel control arm is the benchmark for platinum doublets in BRCA-mutated disease. AbbVie did not seek approval. UK sites (registry, 4): Bristol, Hull, Nottingham, University Hospitals Birmingham.