In BRCA1/2-mutated, HER2-negative advanced breast cancer, talazoparib did not significantly improve overall survival (OS) versus chemotherapy according to final OS analysis of the EMBRACA trial. The OS was generally consistent across subgroups including by prior platinum, hormone-receptor status, or line of treatment. Most patients received subsequent systemic treatments, which may have confounded the OS outcome. Toxicities were managed by supportive care medication/dose modifications. Safety was consistent with previous observations. Extended follow-up of patient reported outcomes (PROs) continued to favour talazoparib over chemotherapy. The findings are reported by Dr Jennifer K. Litton of the Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center in Houston, TX, USA and colleagues on 20 August 2020 in the Annals of Oncology.

The authors reported in the study background that previously reported results from this study showed that talazoparib prolong progression-free survival in comparison to chemotherapy (hazard ratio [HR] 0.542, 95% confidence interval [CI] 0.413–0.711; p < 0.0001) and improve PROs in patients with germline BRCA1/2-mutated, HER2-negative advanced breast cancer.

In total 431 patients were randomised in this study, 287 patients to talazoparib and 144 patients to chemotherapy. From randomised patients, 412 patients have been treated; 286 patients received talazoparib and 126 patients received chemotherapy.

Until 30 September 2019, 216 deaths (75.3%) occurred in talazoparib group and 108 deaths (75.0%) occurred in chemotherapy group. Median follow-up was 44.9 and 36.8 months, respectively. The HR for OS with talazoparib versus chemotherapy was 0.848 (95% CI 0.670–1.073; p = 0.17). Median OS was 19.3 months in talazoparib group and 19.5 months in chemotherapy group. Kaplan-Meier survival percentages for talazoparib versus chemotherapy were 71% and 74% at month 12, 42% and 38% at month 24, and 27% and 21% at month 36.

Most patients received subsequent treatments in both groups, with 46.3% of patients in talazoparib group and 41.7% in chemotherapy group who received platinum, while 4.5% patients in talazoparib group and 32.6% in chemotherapy group received a poly(ADP-ribose) polymerase (PARP) inhibitor. By adjusting for subsequent PARP and/or platinum use, HR for OS was 0.756 (95% bootstrap CI 0.503–1.029).

Grade 3 and 4 adverse events occurred in 69.6% patients who received talazoparib and 64.3% patients who received chemotherapy, which is consistent with previous reports. Extended follow-up showed significant overall improvement and delay in time to definitive clinically meaningful deterioration in global health status/quality of life and breast symptoms favouring talazoparib versus chemotherapy (p < 0.01 for all), which is consistent with initial analyses.

The authors concluded that in germline BRCA1/2-mutated, HER2-negative advanced breast cancer, talazoparib did not significantly improve OS over chemotherapy. However, subsequent treatments may have impacted the analysis. Safety was consistent with previous observations. The PROs continued to favour treatment with talazoparib.

This work was sponsored by Medivation, which was acquired by Pfizer Inc. in September 2016.

Reference

Litton JK, Hurvitz SA, Mina LA, et al. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Annals of Oncology; Published online 20 August 2020. DOI: https://doi.org/10.1016/j.annonc.2020.08.2098

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