PARP Inhibitor Increases PFS Over Chemotherapy in Advanced Breast Cancers, Study Finds

A recent study found that the poly (ADP-ribose) polymerase (PARP) inhibitor talazoparib extended progression-free survival (PFS) and improved quality of life over chemotherapies for patients with metastatic human epidermal growth factor 2-negative breast cancer and mutations in the BRCA 1/2 genes.

A recent study found that the poly (ADP-ribose) polymerase (PARP) inhibitor talazoparib extended progression-free survival (PFS) and improved quality of life over chemotherapies for patients with metastatic human epidermal growth factor 2 (HER2)-negative breast cancer and mutations in the BRCA 1/2 genes.

The results of the EMBRACA trial, an international randomized phase 3 study led by researchers at the University of Texas MD Anderson Cancer Center, were recently published in The New England Journal of Medicine.

Researchers enrolled 431 patients with locally advanced or metastatic and hereditary BRCA1/2 gene mutations in the study. Participants were randomized 2:1 to receive either talazoparib (n = 287) or a physician’s choice of single-agent therapy (n = 144), which was either capecitabine, eribulin, gemcitabine, or vinorelbine. Of the patients enrolled in the trial, 54% had hormone receptor (HR) positive disease, 46% had triple negative breast cancer, and BRCA1 and BRCA2 mutations were split at 45% and 55%, respectively.

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“The trial found that talazoparib provides a significant clinical benefit to all patient subgroups, including those with hormone receptor-positive and triple negative disease,” Jennifer Litton, MD, associate professor of Breast Medical Oncology and the corresponding author of the study, said in a statement. “The results of this trial are quite exciting and indicate talazoparib is a novel treatment option for patients with metastatic breast cancer and BRCA mutations.”

Notably, the primary endpoint of PFS was met in the talazoparib arm as the median PFS was 8.6 months in the talazoparib cohort and 5.6 months in physician’s choice.

Researchers evaluated time to deterioration of overall health as the secondary endpoint of the study. Patient-reported quality of life measures found a greater time to deterioration of overall health in the talazoparib arm, 24.3 months, compared with 6.3 months in the physician’s choice arm.

“It is encouraging to see this oral PARP inhibitor was well-tolerated and superior to chemotherapy alone,” said Litton. To follow-up the positive results of this trial, researchers have already begun a phase 1 study evaluating talazoparid combination treatment.

Reference

Litton J, Rugo H, Ettl J, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation [published online August 15, 2018]. doi: 10.1056/NEJMoa1802905.