PARP inhibitors are unique molecules targeting only the PARP enzyme in BRCA 1/2 mutated cells, they are generally well tolerated as compared to chemotherapy. In this year at San Antonio Breast Cancer Symposium, the EMBRACA trial results were presented in abstract form.
The talazoparib arm patients reported better quality of life score as well as there was a significant delay in the time to deterioration
Talazoparib is a dual-mechanism PARP inhibitor that inhibits the PARP enzyme and also traps PARP on DNA such mechanism specifically target BRCA1 or BRCA2 mutated cells.This was a phase III clinical trial open-label, randomized, 2-arm, phase 3 trial comparing the efficacy and safety of Talazoparib vs physician-choice (PC arm) of standard single-agent chemotherapy in HER2 negative and BRCA1/2 positive patients. The study design overview is shown below.
Result: The study met its endpoint with the following noted,
- The median progression-free survival was 8.6 months for patients in the talazoparib arm, vs 5.6 months for those in the PC arm (HR = 0.542, P < .0001).
- The overall response rate was 62.6% for patients in the talazoparib arm, vs 27.2% for those in the PC arm (HR = 4.99, P < .0001).
- Time to clinical deterioration was 24.3 months for patients on talazoparib, vs 6.3 months for those on standard-of-care chemotherapy.
- About 55% of patients in the talazoparib arm experienced grade 3-4 hematologic adverse events, vs 39% of those in the PC arm.
The clinical benefit was noted in all subgroups including hormone positive patients, and patient with CNS metastases. The talazoparib arm patients reported better quality of life score as well as there was a significant delay in the time to deterioration in global health status. The study investigators concluded efficacy of talazoparib as well as safety and tolerability.
Comments, while this was presented in abstract form, it is a very welcome addition to our understanding and treatment of BRCA1/2 positive advanced breast cancer. At the time of this post, there is 3 FDA approved PARP inhibitors in use in ovarian cancer, no PARP inhibitor is yet approved for breast cancer.