In the BROCADE3 study conducted in patients with gBRCA-associated advanced breast cancer, the addition of veliparib to carboplatin plus paclitaxel with continuation of veliparib monotherapy at intensified dose and schedule if chemotherapy was withdrawn prior to disease progression led to improved progression-free survival (PFS) in patients with hormone receptor (HR)-positive disease and in patients with triple negative breast cancer (TNBC). In both subgroups, benefit of veliparib was durable with an increased probability of remaining progression free at 2 and 3 years compared with placebo. The overall toxicity profile was not substantially different between treatments arms and was generally comparable in the HR-positive and TNBC subgroups according the presentation given by Dr Jean-Pierre Ayoub of the Oncology Department, Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada during the ESMO Breast Cancer Virtual Meeting 2020 (23-34 May).
Dr Ayoub explained that BROCADE3 (NCT02163694) is the first phase III trial to evaluate PARP inhibition in combination with platinum-based chemotherapy for patients with advanced BRCA-associated breast cancer. The results previously reported at ESMO 2019 Congress showed that addition of the PARP1/2 inhibitor veliparib to carboplatin-paclitaxel significantly prolonged PFS in patients with HER2-negative locally advanced/metastatic gBRCA-associated breast cancer (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.57, 0.88, p = 0.002). The study team reported at ESMO Breast Cancer Virtual Meeting 2020 the efficacy and safety in HR-positive and TNBC subgroups separately.
Patients with 2 prior lines of cytotoxic therapy for metastatic breast cancer were randomised 2:1 to veliparib plus carboplatin-paclitaxel or placebo plus carboplatin-paclitaxel. Patients who discontinued carboplatin and paclitaxel prior to progression at investigator discretion received blinded single-agent veliparib or placebo until progression. Primary endpoint was investigator-assessed PFS. Analysis of PFS in subgroups defined by hormone receptor status was preplanned. Analyses of PFS and overall survival (OS) were stratified by prior platinum status.
Among the 509 patients in the intent-to-treat population, there were 266 patients (52%) with HR-positive tumour and 243 patients (48%) had TNBC.
Median PFS per investigators in HR-positive subgroup was 13 months in patients treated with veliparib plus carboplatin-paclitaxel vs 12.5 months in the placebo plus carboplatin-paclitaxel arm (HR 0.69; CI 0.52, 0.93, p = 0.013). Median PFS in TNBC group was 16.6 months in veliparib plus carboplatin-paclitaxel arm vs 14.1 months in placebo plus carboplatin-paclitaxel arm (HR 0.72; CI 0.52, 1.00, p = 0.051).
Median OS per investigators in HR-positive subgroup was 32.4 months in patients treated with veliparib plus carboplatin-paclitaxel vs 27.1 months in the placebo plus carboplatin-paclitaxel arm (HR 0.96; CI 0.68, 1.36). Median OS in TNBC group was 35.0 months in veliparib plus carboplatin-paclitaxel arm vs 30.0 months in placebo plus carboplatin-paclitaxel arm (HR 0.92; CI 0.62, 1.36).
Adverse events, not related to progression led to study drug discontinuation in 8.0%/3.3% of HR-positive patients and 10.5%/7.5% of TNBC patients in the veliparib plus carboplatin-paclitaxel and placebo plus carboplatin-paclitaxel arms, respectively.
Dr Suzette Delaloge of the Gustave Roussy in Villejuif, France, who discussed the study results said that BROCADE3 suggests PFS benefit of approximately 1.5-2 months from veliparib in both HR-positive and TNBC subgroups. Toxicity profile is not very different between the arms. The patients had very good PFS and impressive OS. Although not demonstrating it, BROCADE3 suggests that maintenance approach could be of interest in BRCA-related metastatic breast cancer.
The study was funded by AbbVie Inc.
Abstract 140O – Ayoub J-P, Friedlander ML, Dieras VC, et al. Veliparib plus carboplatin-paclitaxel in patients with HER2-negative advanced/metastatic gBRCA-associated breast cancer: Results in hormone receptor-positive and triple-negative breast cancer subgroups from the phase III BROCADE3 trial. ESMO Breast Cancer Virtual Meeting 2020 (23-24 May 2020).