Veliparib-carboplatin-paclitaxel combo improves PFS in HR+ or TNBC

Adding veliparib to a carboplatin-paclitaxel combination improved progression-free survival (PFS) in patients with BRCA1/2 hormone receptor-positive (HR+) or triple-negative breast cancer (TNBC), subgroup analysis of the phase III BROCADE3* trial showed.

The overall study population comprised 513 patients with locally advanced/metastatic HER2-negative and BRCA1/2 breast cancer who had received ≤2 prior lines of cytotoxic therapy for metastatic disease and had no progression within 12 months of ≤1 platinum therapy. They were randomized 2:1 to receive carboplatin (AUC 6 on day 1) plus paclitaxel (80 mg/m² on days 1, 8, and 15) with either veliparib (120 mg BID on days -2 to 5) or placebo** for 21-day cycles.

Fifty-two percent (n=174 and 92 in the veliparib and placebo groups, respectively) of the population had HR+ tumours, while 48 percent (n=163 and 80, respectively) had TNBC.

Overall results, presented at ESMO 2019, demonstrated improved PFS with the addition of veliparib vs placebo (median 14.5 vs 12.6 months; hazard ratio [HR], 0.705; p=0.002). [ESMO 2019, abstract LBA9]

This improvement was consistent in the subgroup analysis of patients with HR+ disease (median 13.0 vs 12.5 months [veliparib vs placebo]; HR, 0.69, 95 percent confidence interval [CI], 0.52–0.93; p=0.013; 2-year PFS: 27.5 percent vs 15.3 percent, 3-year PFS: 17.5 percent vs 8.6 percent) and TNBC (median 16.6 vs 14.1 months; HR, 0.72, 95 percent CI, 0.52–1.00; p=0.051; 2-year PFS: 40.4 percent vs 25.0 percent, 3-year PFS: 35.3 percent vs 13.0 percent). [ESMO Breast Cancer 2020, abstract 140O]

Overall survival did not significantly differ with veliparib vs placebo in the HR+ (median 32.4 vs 27.1 months; HR, 0.96; p=0.829) or TNBC cohorts (median 35.0 vs 30.0 months; HR, 0.92; p=0.683).

Forty-seven and 28 placebo recipients in the HR+ and TNBC cohorts, respectively, crossed over to receive veliparib monotherapy.

“[T]he 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plus paclitaxel with continuation of veliparib monotherapy at intensified dose and schedule if chemotherapy was withdrawn prior to disease progression led to improved PFS in patients with HR+ disease [or] TNBC,” said Dr Jean-Pierre Ayoub from the Centre Hospitalier de l’Université de Montréal, Quebec, Canada, at ESMO Breast Cancer 2020.

“In both subgroups, benefit of veliparib was durable with an increased probability of remaining progression free at 2 and 3 years compared with placebo,” he said.

Serious adverse events (AEs) were reported in 33.9 and 29.7 percent of veliparib and placebo recipients, respectively, in the HR+ group, and 34.6 and 27.5 percent, respectively, in the TNBC group. The most frequent grade ≥3 AEs in all groups were neutropenia, anaemia, thrombocytopenia, and leukopenia. Study drug discontinuation unrelated to disease progression occurred in 8.0 and 3.3 percent of veliparib and placebo recipients, respectively, in the HR+ group, and 10.5 and 7.5 percent, respectively, in the TNBC group.

“The overall toxicity profile was not substantially different between treatment arms and was generally comparable in the subgroups of patients with HR+ disease and with TNBC,” said Ayoub.

According to discussant Associate Professor Suzette Delaloge from the Institute Gustave Roussy, Paris, France, BROCADE3 suggests a 1.5–2-month PFS benefit with veliparib in both HR+ and TNBC patients. “Although not demonstrating it, BROCADE3 suggests that maintenance approaches could be of interest in BRCA-related metastatic breast cancer,” she noted.