“In both subgroups, the benefit of veliparib was durable, with an increased probability of remaining progression free at 2 and 3 years compared with placebo,”
When administered with carboplatin and paclitaxel,the PARP inhibitor veliparib increased progression-free survival (PFS) in patients with hormone receptor–positive breast cancer and triple-negative breast cancer (TNBC) who were positive for germline BRCA1/2 mutations. These findings from the phase 3 BROCADE3 trial (NCT02163694) were reported at the 2020 European Society for Medical Oncology Breast Cancer Virtual Meeting. In the hormone receptor–positive subset of patients treated with veliparib, carboplatin, and paclitaxel (n =174),the 2-year and 3-year PFS rates by investigator assessment were 27.5% and 17.5%, respectively. Among the 92 patients with hormonereceptor–positive disease randomized to carboplatin/paclitaxel, the 2-year rate of PFS was 15.3% and the 3-year rate of PFS was 8.6%. The median PFS was 13.0 months with the 3-drug approach versus 12.5 months with carboplatin and paclitaxel alone (HR, 0.69; 95% CI, 0.52-0.93; 2-sided P =.013).
“In both subgroups, the benefit of veliparib was durable, with an increased probability of remaining progression free at 2 and 3 years compared with placebo,” saidJean-Pierre Ayoub, MD,lead author of the study and an assistant clinical professor in the Department of Medicine at the Université de Montréal in Quebec, Canada.
The trimodality also led to a superior survival benefit in patients with TNBC. The 2-year investigator- assessed PFS rate was 40.4% compared with 25.0% with carboplatin and paclitaxel. The 3-year rate of PFS also favored veliparib plus carboplatin/paclitaxel. “It’s impressive to see [that] at 3 years in the veliparib arm, 35.3% of patients in this poor prognostic, triple- negative subgroup are progression free compared [with] 13.0% in the placebo arm,” Ayoub said.
In this subgroup, the median PFS was 16.6 months (95% CI, 12.3-22.7) in the veliparib, carboplatin, and paclitaxel arm and 14.1 months (95% CI, 11.0-15.8) with chemotherapy (HR, 0.72; 95% CI, 0.52-1.00; 2-sided P = .051).
These subgroup-specific findings build on the survival benefit observed in the intention-to-treat (ITT) population, in which the investigator-assessed median PFS was 14.5 months with the veliparib regimen and 12.6 months with chemotherapy (HR, 0.705; 95% CI, 0.566-0.877; P = .002).
Overall survival (OS) in the study, which enrolled 509 patients, was similar across subgroups, Ayoub said. The median OS was 32.4 months on the veliparib arm and 27.1 months with chemotherapy in the hormone receptor–positive subgroup (HR, 0.96; 95% CI, 0.681.36; 2-sided P = .829). Among patients with TNBC, the median OS was 35.0 months with the 3-drug regimen versus 30.0 months with carboplatin and paclitaxel (HR, 0.92; 95% CI, 0.62-1.36; 2-sided P = .683).
Neither P value was significant, according to Ayoub, who also noted that adding veliparib did not improve the objective response rate or clinical benefit rate in either subgroup. However, he noted that responses appeared more durable in the veliparib arms. “This may account for the difference that you see in median PFS to a likely carryover effect of the veliparib-treated patients, where we see improvement in PFS to 20.3 months in hormone receptor–positive versus 16.6 months in the placebo arm,” he said.
The overall toxicity profile “was not substantially different between the treatment arms and was generally comparable in the subgroups of patients with hormone receptor–positive disease and triple-negative breast cancer,” Ayoub said. Additionally, safety in the hormone receptor–positive and TNBC subgroups was similar in the ITT population.
In both subgroups, the incidence of any-grade anemia, neutropenia, nausea, and diarrhea was increased by more than 5% in the veliparib arm versus the chemotherapy arm. Although there were some differences between the subgroups, they were not directionally consistent. Neutropenia (78.2%), anemia (40.8%), thrombocytopenia (35.6%), leukopenia (32.2%), and fatigue (6.3%) were the 5 most common grade 3 or higher adverse effects observed in veliparib-receiving patients with hormone receptor–positive disease. This f inding was consistent in the veliparib-treated TNBC group, in which these toxicities affected 84.0%, 44.4%, 43.8%, 25.9%, and 8.0% of patients, respectively.
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. Ann Oncol. 2020;31(suppl 2):140O. doi:10.1016/j.annonc.2020.03.241