Addition of Veliparib to Carboplatin-Paclitaxel Increases PFS in HR+ Breast Cancer, TNBC

Article

The PARP inhibitor veliparib increased progression-free survival in women with hormone receptor-positive breast cancer and triple-negative breast cancer who harbored a germline BRCA1/2 mutation when co-administered with carboplatin and paclitaxel, according to findings from the phase 3 BROCADE3 trial (NCT02163694).

Jean-Pierre Ayoub, MD

Jean-Pierre Ayoub, MD

Jean-Pierre Ayoub, MD

The PARP inhibitor veliparib increased progression-free survival (PFS) in women with hormone receptor (HR)-positive breast cancer and triple-negative breast cancer (TNBC) who harbored a germline BRCA1/2 mutation when co-administered with carboplatin and paclitaxel, according to findings from the phase 3 BROCADE3 trial (NCT02163694), presented during the 2020 ESMO Breast Cancer Virtual Meeting.

“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,” said Jean-Pierre Ayoub, MD, lead author of the BROCADE3 study and an assistant professor in the Department of Medicine at the University of Montreal in Montreal, France.

In the HR-positive subset of patients treated with veliparib, carboplatin, and paclitaxel (n = 174), the 2 year and 3 year PFS by investigator assessment was 27.5% and 17.5%, respectively. Among the 92 HR-positive patients randomized to carboplatin and paclitaxel, the 2 year PFS was 15.3% and the 3 year 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).

The tri-modality also led to a superior survival benefit in patients with TNBC. The 2 year, investigator-assessed PFS was 40.4% compared with 25.0% with carboplatin and paclitaxel. The 3 year PFS also favored veliparib, carboplatin, and 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 intent-to-treat population, where the investigator-assessed median PFS was 14.5 months with the veliparib-containing regimen and 12.6 months with chemotherapy (HR, 0.705; 95% CI, 0.566-0.877; P = .002).

Overall Survival

Overall survival (OS) in the BROCADE3 study, which enrolled 509 patients, was similar across subgroups, said Ayoub. The median OS was 32.4 months with veliparib, carboplatin, and paclitaxel and 27.1 months with chemotherapy in the HR-positive subgroup (HR, 0.96; 95% CI, 0.68-1.36; 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 the addition of veliparib did not improve the objective response rate or clinical benefit rate in either patient subgroup. However, responses “appeared to be more durable in the veliparib arms,” said Ayoub. “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.”

The Triplet Demonstrates Tolerability

The overall toxicity profile “was not substantially different between the treatment arms and was generally comparable in the subgroups of patients with HR-positive disease and triple-negative breast cancer,” Ayoub said. Additionally, safety in the HR-positive and TNBC subgroups was similar in the intent-to-treat population.

In both subgroups, the incidence of any-grade anemia, neutropenia, nausea, and diarrhea was increased by more than 5% in the veliparib arms versus the chemotherapy arms. 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 events observed in veliparib-receiving HR-positive patients. This finding was consistent in the veliparib-treated TNBC group, where 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. Presented at: 2020 ESMO Breast Cancer Virtual Meeting; May 22-23, 2020. Abstract 140O.

<<< 2020 ESMO Breast Cancer Virtual Meeting

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