Adding veliparib to carboplatin and paclitaxel for patients with advanced BRCA mutation-associated breast cancer is safe but did not improve survival, according to findings from a phase 2 BROCADE (ClinicalTrials.gov Identifier: NCT01506609) trial presented at the 2016 San Antonio Breast Cancer Symposium.
Veliparib did not affect the safety profile, frequency of interruption, dose reduction rate, or discontinuation rate, reported Hyo-Sook Han, MD, of the Moffitt Cancer Center in Tampa, Florida.
Approximately half of women who inherit a BRCA1/2 mutation will develop breast cancer before the age of 70 years, she noted. These cancers are “particularly sensitive” to poly(ADP-ribose) polymerase (PARP) inhibitors, which disrupt DNA repair.
“Emerging clinical data indicate that patients with BRCA mutations may also be particularly sensitive to platinum-containing therapies,” she said.
Veliparib is an oral selective PARP-1 and PARP-2 inhibitor and, in combination with carboplatin, improves pathologic complete response (pCR) rates when added to standard neoadjuvant treatment.
The research team enrolled 290 women with locally recurrent or metastatic breast cancer with BRCA1/2 mutations, stratifying patients by estrogen receptor (ER) and progesterone receptor (PR) status, prior cytotoxic therapy, and ECOG performance status. The patients were randomly assigned 1:1:1 to receive carboplatin (AUC 6) and paclitaxel (175mg/m2) every 3 weeks plus either placebo or veliparib (120mg twice daily on days 1-7), or veliparib (40mg) plus temozolomide. (The temozolomide group results were not presented in Dr Han’s talk.)
All veliparib group patients and 97.9% of placebo patients experienced adverse events. Serious adverse events were reported for 27% of placebo-group patients and 34% of veliparib group patients. Common hematologic toxicities, similar in both groups, included anemia, leukopenia, neutropenia, and thrombocytopenia.
Tumor objective response rates (ORRs) were 61% for placebo and 77.8% for veliparib (P = 0.027).
Neither progression-free survival (PFS) nor overall survival (OS) was different from placebo for patients receiving veliparib, Dr Han reported. (Median PFS for placebo vs veliparib: 12.3 vs 14.1 months; hazard ratio [HR], 0.789; P = 0.23; median OS: 25.9 vs 28.3 months, HR, 0.75; P = 0.157). The prespecified number of OS events had, however, not yet been reached, so a final OS analysis has not yet been performed, Dr Han noted.
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“Further evaluation of the efficacy and safety of veliparib with weekly paclitaxel and carboplatin in patients with BRCA-mutated advanced breast cancer is ongoing in the phase 3 randomized trial BROCADE3,” she concluded.
- Han HS, Dieras V, Robson ME, et al. Efficacy and tolerability of veliparib (V; ABT-888) in combination with carboplatin (C) and paclitaxel (P) vs placebo (Plc)+C/P in patients (pts) with BRCA1 or BRCA2 mutations and metastatic breast cancer: A randomized, phase 2 study. Paper presented at: 39th San Antonio Breast Cancer Symposium; Dec 2016; San Antonio, TX.