Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): Final overall survival results from a randomized phase 3 trial

• Published in: European journal of cancer (1990) Vol. 200; p. 113580
• Main Authors: Diéras, Véronique, Han, Hyo S., Wildiers, Hans, Friedlander, Michael, Ayoub, Jean-Pierre, Puhalla, Shannon L., Loirat, Delphine, Ratajczak, Christine, Adamu, Hephzibah, Girardi, Vincent, Arun, Banu K.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2024
• Subjects: Antineoplastic Combined Chemotherapy Protocols - adverse effects; Benzimidazoles; BRCA1; BRCA1 Protein - genetics; BRCA2; BRCA2 Protein - genetics; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; BROCADE3; Carboplatin; Female; HER2-negative; Humans; Overall survival; Paclitaxel; Progression-free survival; Veliparib; HER2-negative; Veliparib; Breast cancer; BRCA1; BRCA2; Overall survival; Progression-free survival; BROCADE3
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2024.113580

In the BROCADE3 study, the addition of veliparib to carboplatin plus paclitaxel resulted in a significant improvement in progression-free survival (PFS) compared with placebo plus carboplatin and paclitaxel, in patients with germline BRCA1 or BRCA2 (BRCA1/2)-mutated, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We now report final overall survival (OS) data. BROCADE3 is a randomized phase 3 study that enrolled patients with BRCA1/2-mutated, HER2-negative advanced breast cancer who received ≤ 2 prior lines of chemotherapy for metastatic disease. Patients were randomized 2:1 to carboplatin and paclitaxel, dosed with either veliparib or matching placebo. OS was a secondary endpoint. In the intention-to-treat population (N = 509), 337 patients were randomized to receive veliparib and 172 to placebo. Median OS was 32.4 months vs 28.2 months (hazard ratio, 0.916; 95% CI, 0.736–1.140; P = .434). The updated safety data for veliparib are consistent with those reported in the primary analysis; the addition of veliparib was generally well tolerated. Final OS data indicate that the PFS improvement shown in the primary analysis did not translate into an OS benefit. The long survival times observed in both arms suggest that combination therapy with paclitaxel and carboplatin provides clinical benefit in the population of patients with BRCA1/2-mutated metastatic breast cancer. •Veliparib is a potent, orally bioavailable, selective PARP-1 and PARP-2 inhibitor.•BROCADE3 assessed veliparib with chemotherapy for BRCA mutated advanced breast cancer.•Addition of veliparib to carboplatin/paclitaxel significantly improved PFS.•However, there was no benefit at the final overall survival analysis.•Durable survival times suggest the combinatorial approach is beneficial.