Efficacy and safety of first-line veliparib and carboplatin–paclitaxel in patients with HER2− advanced germline BRCA+ breast cancer: Subgroup analysis of a randomised clinical trial

• Published in: European journal of cancer (1990) Vol. 154; pp. 35 - 45
• Main Authors: Arun, Banu K., Han, Hyo S., Kaufman, Bella, Wildiers, Hans, Friedlander, Michael, Ayoub, Jean-Pierre, Puhalla, Shannon L., Bell-McGuinn, Katherine M., Bach, Bruce A., Kundu, Madan G., Ratajczak, Christine K., Maag, David, Diéras, Véronique
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2021; Elsevier Science Ltd
• Subjects: Adult; Adverse events; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Benzimidazoles - administration & dosage; Benzimidazoles - adverse effects; BRCA; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Carboplatin; Carboplatin - administration & dosage; Carboplatin - adverse effects; Chemotherapy; Confidence intervals; Cytotoxicity; Disease control; Effectiveness; ErbB-2 protein; Female; Genes, BRCA1; Genes, BRCA2; Germ-Line Mutation; Humans; Metastases; Metastasis; Middle Aged; Paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; PARP inhibitor; Patients; Placebos; Receptor, ErbB-2 - analysis; Safety; Subgroups; Therapy; BRCA; Chemotherapy; Breast cancer; PARP inhibitor
• ISSN: 0959-8049; 1879-0852; 1879-0852
• DOI: 10.1016/j.ejca.2021.05.037

Addition of veliparib to carboplatin–paclitaxel, with continuation of veliparib monotherapy if carboplatin–paclitaxel was discontinued, improved progression-free survival (PFS) in patients with germline BRCA-associated locally advanced/metastatic HER2− breast cancer and ≤2 lines of previous cytotoxic therapy for metastatic disease in BROCADE3. A pre-planned subgroup analysis evaluated efficacy and safety in patients without previous cytotoxic therapy for metastatic disease. Patients were randomised 2:1 to receive veliparib (120 mg orally BID) or placebo on days −2 to 5. Carboplatin (AUC 6) was administered on day 1, and paclitaxel (80 mg/m2) on days 1, 8 and 15 (21-day cycles). Patients discontinuing carboplatin–paclitaxel for reasons besides progression could continue veliparib/placebo monotherapy (300 mg BID, increasing to 400 mg BID if tolerated) until progression. The primary end-point was PFS assessed by investigator. Of 509 patients in the intention-to-treat population (98.6% female; mean age 47, standard deviation 11), 413 (81%) had no previous cytotoxic therapy for metastatic disease (274, veliparib; 139, placebo). In the first-line subgroup, median PFS was 16.6 months (95% confidence interval [CI] 13.4–18.7) versus 13.1 months (95% CI 11.4–14.5) for the veliparib versus control groups (hazard ratio 0.70, 95% CI 0.54–0.89, P = .004). More patients were alive and progression-free at 2 years (36% versus 23.2%) and 3 years (27.9% versus 13.3%) in the veliparib versus control group. Adverse events unrelated to progression leading to study drug discontinuation occurred in 25 (9.1%) and 8 (5.8%) patients. Veliparib with carboplatin–paclitaxel led to durable disease control among first-line patients, suggesting a benefit of this treatment approach in early lines. NCT02163694. •BROCADE3 showed veliparib plus platinum efficacy for BRCA+ advanced breast cancer.•This subanalysis was in patients without prior chemotherapy for metastatic disease.•Addition of veliparib to carboplatin–paclitaxel led to durable disease control.•The data suggest a benefit of veliparib plus platinum in early lines of therapy.