Phase 3 EMBRACA Findings Suggest No Overall Survival Benefit With Talazoparib in Advanced BRCA-Mutated Breast Cancer

April 28, 2020

In new data from the phase 3 EMBRACA trial presented yesterday at the American Association for Cancer Research annual meeting, researchers found that PARP inhibitor talazoparib exhibited no statistically significant benefit in the secondary end point of overall survival in patients with metastatic HER2-negative breast cancer and mutations in the BRCA1/2 genes.

In new data from the phase 3 EMBRACA trial presented yesterday at the American Association for Cancer Research (AACR) annual meeting, researchers found that PARP inhibitor talazoparib exhibited no statistically significant benefit in the secondary end point of overall survival (OS) in patients with metastatic HER2-negative breast cancer and mutations in the BRCA1/2 genes. However, OS findings may have been understated as most patients included in the study went on to receive subsequent systemic therapies.

EMBRACA is the largest trial to date examining PARP monotherapy in patients with germline BRCA-mutated HER2-negative advanced breast cancer. Previously, the trial’s primary analysis found that patients treated with talazoparib experienced significantly prolonged progression-free survival (PFS) compared with chemotherapy (median PFS of 8.6 months vs 5.6 months), which led to its FDA approval in 2018.

While PFS exhibited substantial benefits from talazoparib, OS can prove a challenge for patients with metastatic breast cancer due to the availability of numerous treatment options, notes Jennifer Litton, MD, professor of Breast Medical Oncology, who presented results during AACR. The trial randomized 431 patients (2:1) with locally advanced or metastatic and hereditary BRCA1/2 gene mutations to receive either talazoparib (n = 287) or physician's choice of treatment (PCT) of single-agent therapy (n = 144), including capecitabine, eribulin, gemcitabine, or vinorelbine.

In the trial, nearly half of patients in the talazoparib group received a subsequent PARP inhibitor or platinum therapy compared with almost 60% of patients in the chemotherapy group. When stratified for only those receiving PARP inhibitors, approximately one-third of patients in the chemotherapy group received a subsequent PARP inhibitor compared with only 4.5% of those administered talazoparib.

The subsequent treatments provided were highlighted by Litton as she described how they may have potentially influenced results. In fact, after carrying out 2 sensitivity analyses to account for subsequent PARP inhibitor and/or platinum therapy, data suggest that the OS analysis underestimated the treatment benefit of talazoparib.

Aligned with findings from the primary analysis, patient-reported quality-of-life measures were improved among those administered talazoparib compared with chemotherapy as shown by a prolonged time to deterioration of overall health (26.3 months in the talazoparib group vs 6.7 months in the chemotherapy group).

“Talazoparib remains an option for patients with advanced breast cancer and a germline BRCA mutation due to its improvements in progression free survival,” said Litton. “Other advantages include it being an oral once-daily option, as well as the demonstrated improvements in quality of life for metastatic breast cancer patients.”