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

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/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.

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.

Keywords: BRCA; Breast cancer; Chemotherapy; PARP inhibitor.

Conflict of interest statement

Conflict of interest statement BK Arun has received research support to her institution from AbbVie, PharmaMar, Astra Zeneca and Invitae, and is a Steering Committee (non-paid) member for AbbVie. HS Han has received research funding to her institution from AbbVie, Arvinas, Prescient, Horizon, Karyopharm, BMS, Novartis, Pfizer, GSK, Marker Therapeutics, Seattle Genetics and Zymeworks. She has received a grant from the Department of Defense and is on the speakers’ bureau for Lilly. B Kaufman is an Advisory Board member for AbbVie, Astra Zeneca, Roche, Novartis and Pfizer. H Wildiers’ institution received consulting fees and honoraria from Roche, Astra Zeneca, Amgen, Lilly, Novartis, AbbVie, Vifor Pharma, Pfizer, Celldex Therapeutics, Janssen-CILAG, TRM Oncology, PUMA Biotechnology, ORION Corporation and an unrestricted research grant from Roche. He received travel support from Roche and Pfizer. M Friedlander reports a consulting/advisory role for AstraZeneca, MSD, AbbVie, Lilly, Takeda and Novartis. He is on the speakers’ bureau for AstraZeneca. He has received honoraria from AstraZeneca, MSD, Lilly, Takeda, Novartis and GSK, and has received research funding from BeiGene, AstraZeneca and Novartis. JP Ayoub has received research funding to his instituion from AbbVie and Boston Biomedical. He is a consultant for Astra Zeneca, Eisai, Eli Lilly, Novartis, Pfizer, Puma and Roche. SL Puhalla is a consultant for AbbVie, MedImmune, Celldex, Puma, Pfizer, AstraZeneca, Eisai and Nanostring. She has received research funding to her institution from AbbVie, Pfizer, Lilly, Novartis, Incyte, Covance-Bayer, Astra Zeneca, Genentech and Medivation. VC Diéras reports a consulting/advisory role to Roche/Genentech, Novartis, Lilly, Pfizer, Astellas, AbbVie, MSD, Tesaro, Daiichi Sankyo, Odonate, Seattle Genetics and Astra Zeneca. KM Bell-McGuinn, BA Bach, CK Ratajczak and D Maag are AbbVie employees and own stock. M Kundu is a former AbbVie employee and may own stock.

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.