At the recent American Association for Cancer Research (AACR) Virtual Annual Meeting I 2020, the final overall survival (OS) results of the phase III EMBRACA trial (ClinicalTrials.gov Identifier: NCT01945775) were presented. These findings indicated that the poly(adenosine diphosphate–ribose) (PARP) inhibitor, talazoparib (TALA) failed to demonstrate an OS benefit when compared with physician’s choice of chemotherapy (PCT) in patients with HER2-negative advanced breast cancer who have a germline BRCA1/2 mutation. 

The EMBRACA is the largest trial to date examining PARP monotherapy in patients with germline BRCA-mutated HER2-negative advanced breast cancer. A previous analysis of the EMBRACA trial indicated 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 with locally advanced or metastatic and hereditary BRCA1/2 gene mutations to receive either talazoparib (287 patients) or PCT (144 patients) of single-agent therapy, including capecitabine, denibulin, gemcitabine, or vinorelbine. HR was based on stratified Cox regression model (treatment as covariate); P value on stratified log-rank test. 

The talazoparib arm was followed for a median of 44.9 months and the chemotherapy arm for 36.8 months. By September 30, 2019, 216 deaths (75.3%) occurred for TALA and 108 deaths (75.0%) for PCT; median follow-up was 44.9 and 36.8 months, respectively. HR for OS was 0.85 (95% CI, 0.67-1.07; P = .17); survival probability was higher for patients receiving TALA at 24, 36, and 48 months. The final OS analysis revealed that among the intention-to-treat population, those who received talazoparib did not live substantially longer compared with those who received chemotherapy. 

The study presenter, Jennifer K. Litton, MD, of The University of Texas MD Anderson Cancer Center, Houston said, “It is important to note that most patients in this study went on to receive subsequent therapies, which may have confounded the survival analysis.”

The majority of patients received poststudy therapies; 32.6% of patients in the PCT arm received a PARP inhibitor post study (4.5% for TALA arm). Grade 3-4 adverse events occurred in 69.6% (TALA) and 64.3% (PCT) patients. Adverse events leading to permanent treatment discontinuation (excluding progressive disease) occurred in 5.9% and 8.7% of patients. 

Extended follow-up demonstrated statistically significant overall improvements and delays in time to definitive clinically meaningful deterioration in both global health status/QoL and breast symptoms scales favoring TALA versus PCT (P <.01 for all), consistent with initial PRO analyses. The researchers concluded that in gBRCA1/2-mutated HER2-ABC, TALA did not considerably improve OS over PCT (HR, 0.85; 95% CI, 0.67-1.07; P = .17). The analysis was not modified for subsequent therapies. TALA was usually well-tolerated with no new safety signals. Improved patient-reported outcomes continued to favor TALA.                                                                                                                                                                                                                                  
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