Talazoparib failed to show an overall survival (OS) benefit when compared with physician’s choice of chemotherapy in patients with HER2-negative advanced breast cancer who have a germline BRCA1/2 mutation, according to the final OS analysis of the phase 3 EMBRACA trial (ClinicalTrials.gov Identifier: NCT01945775). Trial results were recently presented at the American Association for Cancer Research (AACR) Virtual Annual Meeting I 2020.
A previous analysis of the EMBRACA trial showed a longer progression-free survival for talazoparib compared with chemotherapy (hazard ratio [HR], 0.54; 95% CI, 0.41-0.71; P <.001).
For the EMBRACA trial, 431 patients were randomly assigned in a 2:1 fashion to receive either talazoparib (287 patients) or physician’s choice of chemotherapy (144 patients). The talazoparib arm was followed for a median of 44.9 months and the chemotherapy arm 36.8 months.
The final OS analysis showed that among the intention-to-treat population, those who received talazoparib did not live significantly longer compared with those who received chemotherapy (HR, 0.85; 95% CI, 0.67-1.07; P =.17).
“It is important to note that most patients in this study went on to receive subsequent therapies, which may have confounded the survival analysis,” said the study presenter Jennifer K. Litton, MD, of The University of Texas MD Anderson Cancer Center, Houston.
Most patients received an antineoplastic therapy after the study. Among patients on the talazoparib arm, 4.5% went on to receive a poly ([ADP]-ribose) polymerase (PARP) inhibitor and 46.3% a platinum-based therapy. In contrast, among patients on the chemotherapy arm, 32.6% went on to receive a PARP inhibitor and 41.7% a platinum-based therapy.
The incidence of grade 3 or 4 serious adverse events was similar between treatment arms: 28.3% for the talazoparib arm and 27.0% for the chemotherapy arm. Adverse events led to permanent treatment discontinuation for 7.7% of patients on the talazoparib arm and 9.5% of patients on the chemotherapy arm.
An exploratory endpoint, the estimated change from baseline in global health status/quality of life was improved for the talazoparib arm (2.1; 95% CI, 0.1–4.1) but declined for the chemotherapy arm (–5.7 [95% CI; –10.0 to –1.4). This difference was statistically significant (P =.001).
In addition, the time to definitive clinically meaningful deterioration in global health status/quality of life was significantly delayed for the talazoparib arm compared with the chemotherapy arm (HR, 0.385; 95% CI, 0.264–0.563).
Litton JK, Hurvitz SA, Mina LA, et al. Talazoparib (TALA) in germline BRCA1/2 (gBRCA1/2)-mutated human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC): Final overall survival (OS) results from randomized phase 3 EMBRACA trial. Presented at: American Association for Cancer Research (AACR) Virtual Annual Meeting I; April 27-28, 2020. Abstract CT071.