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. (September 2021)

• Record Type: Journal Article
• 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
• Is Part Of: European journal of cancer. Volume 154(2021)
• Page Start: 35
• Page End: 45
• Publication Date: 2021-09
• Subjects: PARP inhibitor -- Chemotherapy -- Breast cancer -- BRCA; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2021.05.037
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: 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. Methods: 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/m 2 ) 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. Results: 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. Conclusions: Veliparib with carboplatin–paclitaxel led to durable disease control among first-line patients, suggesting a benefit of this treatment approach in early lines. Clinical trial registration: NCT02163694. Highlights: 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.