Veliparib plus chemotherapy improves BRCA-mutated breast cancer PFS
medwireNews: Combining the PARP inhibitor veliparib with carboplatin and paclitaxel delays disease progression and death in patients with BRCA-mutated, HER2-negative advanced breast cancer, show data from the BROCADE3 trial.
Writing in The Lancet Oncology, Véronique Diéras (Centre Eugène Marquis, Rennes, France) and co-investigators say their findings “suggest that veliparib, in combination with carboplatin and paclitaxel, should be considered as a new treatment option for patients with BRCA-associated advanced breast cancer who are candidates for chemotherapy.”
The phase 3 trial included 509 patients who were randomly assigned to receive either veliparib (120 mg twice daily; n=337) or placebo (n=172) on days −2 to 5 of each 21-day cycle in combination with carboplatin (AUC 6 mg/mL per min, day 1) and paclitaxel (80 mg/m2, days 1, 8, and 15). The majority (81%) had not received prior chemotherapy for metastatic disease.
The majority of patients continued these treatment cycles until disease progression, but a subset (41% and 34% in the veliparib and placebo groups, respectively) discontinued carboplatin and paclitaxel, most commonly after 6 cycles, and continued to receive only veliparib or placebo at an intensified dose (300 mg twice daily continuously, increasing to 400mg twice daily, if tolerated) until disease progression.
The researchers report that, after a median follow-up of nearly 36 months, median progression-free survival (PFS) was significantly longer among patients who received veliparib relative to those who received placebo, at 14.5 versus 12.6 months. This corresponded to a significant 29% lower risk for disease progression or death with veliparib.
The researchers say that the estimated survival curves did not begin to separate until approximately 1 year. By 2 years, however, the PFS rate was 33.6% with veliparib and 19.8% with placebo, and by 3 years the corresponding rates were 25.7% and 10.7%.
There was no significant difference in median overall survival (OS) between the patients who received veliparib and those who received placebo (33.5 vs 28.2 months), but Diéras and team note that the survival data are not yet mature.
Nonetheless, Melinda Telli, from Stanford University in California, USA, points out in an accompanying comment that subgroup analyses showed that median OS was 35 months among patients with triple-negative breast cancer, which she says “represents the best overall survival ever reported for triple-negative breast cancer.”
There were no treatment-related deaths and the rates of discontinuation due to adverse events (AEs) were 16% and 11% in the veliparib and placebo groups, respectively. The most commonly reported AE of grade 3 or worse was neutropenia, occurring in 81% and 84%, respectively, followed by anemia (42 vs 40%) and thrombocytopenia (40 vs 28%).
Diéras et al conclude: “BROCADE3 has shown, we believe for the first time, that the combination of a PARP inhibitor, veliparib, with platinum chemotherapy significantly improves progression-free survival with little additional toxicity in patients with advanced HER2-negative breast cancer and a BRCA mutation.”
Telli says that, although questions regarding optimal treatment duration and sequencing remain unanswered, these findings “force us to consider whether a strategy of platinum-based induction combination chemotherapy followed by PARP inhibitor maintenance, as is standardly used in ovarian cancer, might ultimately lead to superior outcomes for this group of patients.”
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