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AACR 2020: Final Overall Survival Results From the Phase III EMBRACA Trial


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New data from the phase III EMBRACA trial showed the poly (ADP-ribose) polymerase (PARP) inhibitor talazoparib did not produce a statistically significant overall survival benefit for patients with locally advanced or metastatic HER2-negative germline BRCA­-mutated breast cancer. Most patients included in the study went on to receive subsequent systemic therapies, which may have affected the survival outcome analysis. Nevertheless, the research confirmed previous results showing talazoparib improved patient-reported quality-of-life measures over available chemotherapies and had a tolerable safety profile. The secondary endpoint results from the EMBRACA trial were presented at the American Association for Cancer Research (AACR) Virtual Annual Meeting by Jennifer Litton, MD, Professor of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center (Abstract CT017).

Jennifer Litton, MD

Jennifer Litton, MD

The primary analysis results from the trial were previously published by Dr. Litton and colleagues in The New England Journal of Medicine. The data demonstrated that patients treated with talazoparib had a significantly prolonged progression-free survival compared to those treated with chemotherapy—8.6 months vs 5.6 months, respectively. This led to U.S. Food and Drug Administration approval of talazoparib in 2018.

Study Details

EMBRACA is the largest trial of PARP monotherapy to date in patients with germline BRCA-mutated, locally advanced or metastatic HER2-negative breast cancer. The international phase III clinical trial enrolled 431 patients. Patients were allowed up to three previous chemotherapies, including platinum-based therapies.

Participants were randomly assigned 2:1 to receive either talazoparib (n = 287) or physician’s choice of treatment of single-agent therapy (n = 144)—either capecitabine, eribulin, gemcitabine, or vinorelbine. Fifty four percent of participants had hormone receptor–positive disease and 46% had triple-negative breast cancer; BRCA1 and BRCA2 mutations were split at 45% and 55%, respectively.

Overall Survival Analysis

The final overall survival analysis was performed using the intent-to-treat population after 324 deaths had been observed. After a median follow-up of 44.9 months for the talazoparib group and 36.8 months for the chemotherapy group, 216 patients treated with talazoparib and 108 patients treated with chemotherapy had died. The effect of treatment with talazoparib also was similar regardless of BRCA status.

“Overall survival is always an important endpoint, but also a challenge for [patients with] metastatic breast cancer as there are many treatment options available. Many of these patients also received subsequent therapies, including PARP inhibitors and platinum-based therapies, which could have potentially influenced these results.”
— Jennifer Litton, MD

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“Overall survival is always an important endpoint, but also a challenge for [patients with] metastatic breast cancer as there are many treatment options available,” said Dr. Litton. “Many of these patients also received subsequent therapies, including PARP inhibitors and platinum-based therapies, which could have potentially influenced these results.”

Almost 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 looking at PARP inhibitors specifically, approximately one-third of patients in the chemotherapy group received a subsequent PARP inhibitor, which became increasingly available to patients either through trials or commercially during the course of this trial, compared with only 4.5% of patients who received talazoparib.

Subsequent platinum therapy was received by around 46% of patients in the talazoparib group compared with approximately 42% of patients in the chemotherapy group.

Interpretation of the overall survival results may have been confounded by subsequent treatments, so two sensitivity analyses accounting for subsequent PARP inhibitor and/or platinum therapy were carried out. The analysis suggests that the overall survival analysis underestimated the treatment benefit of talazoparib.

Patient-reported quality-of-life measures revealed a prolonged time to deterioration of overall health—26.3 months in the talazoparib arm compared to 6.7 months for the chemotherapy arm.

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

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

Grade 3 or 4 hematologic adverse events occurred in 56.6% of patients receiving talazoparib and 38.9% of those on chemotherapy. Most grade 3 or 4 adverse events reported in the talazoparib group were hematologic and most were successfully managed by supportive care and dose modifications. The most common hematologic adverse event in patients receiving talazoparib was anemia, which was reported in 54.9% of patients receiving talazoparib compared with 19.0% of patients receiving chemotherapy.  

Extended follow-up showed statistically significant overall improvements and delays in time to definitive clinically meaningful deterioration in both global health status/quality-of-life and breast symptom scales favoring talazoparib vs physician’s choice of therapy. These findings were consistent with initial patient-reported outcomes analyses.

The authors concluded, “In germline BRCA1/2-mutated HER2-negative locally advanced or metastatic breast cancer, talazoparib did not significantly improve overall survival over physician’s choice of chemotherapy, analysis not adjusted for subsequent therapies. Talazoparib was generally well-tolerated with no new safety signals. Patient-reported outcomes continued to favor talazoparib.”

Disclosure: For full disclosures of the study authors, visit abstractsonline.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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