Compared with standard chemotherapy, single-agent talazoparib was found to significantly extend progression-free survival in patients with advanced breast cancer and a germline BRCA1/2 mutation, according to a study published in The New England Journal of Medicine.
An international team of investigators conducted an international randomized, open-label, phase 3 clinical trial (EMBRACA; ClinicalTrials.gov Identifier: NCT01945775) to assess the efficacy of talazoparib compared with standard chemotherapy in patients with advanced breast cancer and a germline BRCA1/2 mutation.
A total of 431 patients were included in the analysis. A 2:1 ratio was used to administer talazoparib, 1 mg/d (n = 287) or a standard single-agent therapy (n = 144) such as capecitabine, eribulin, gemcitabine, or vinorelbine in continuous 21-day rotation (single-agent therapies were chosen by physicians).
The talazoparib cohort demonstrated longer progression-free survival compared with the standard-therapy cohort (8.6 months vs 5.6 months, respectively; disease progression or death hazard ratio, 0.54). At 1 year, 37% of patients in the talazoparib cohort and 20% in the standard-therapy cohort did not experience disease progression.
The investigators reported 163 deaths at the time of primary analysis: 108 patients in the talazoparib group and 55 patients in the control group. The median overall survival at interim was 22.3 months for the talazoparib cohort and 19.5 months for the control group (hazard ratio for death, 0.76). Response rates were significantly higher among patients in the talazoparib cohort compared with those in the standard-therapy cohort (62.6% vs 27.2%; odds ratio, 5.0).
“[T]alazoparib resulted in a significantly longer progression-free survival than standard-of-care chemotherapy,” the authors concluded. “Treatment-associated myelotoxicity was managed by dose modifications or delays. Improvements in patient-reported outcomes indicated that talazoparib has a good side-effect profile.”
Disclosure: This study was supported by Medivation, a Pfizer company.
Litton JK, Rugo HS, Ettl J, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018;379(8):753-763.