Top Line: PARP-inhibitors are effective in patients with advanced, BRCA-mutated breast cancer by causing lethal accumulation of DNA damage to tumor cells with pre-existing defects in DNA damage repair.
The Study: In the EMBRACA trial, the addition of the PARP-inhibitor talazoparib resulted in a doubling of the response rate and an increase in progression-free survival among women with metastatic breast cancer. This MD Anderson pilot study evaluates the efficacy of 6 months of talazoparib monotherapy in the neoadjuvant setting for women with stage I-III (at least 1 cm), germline BRCA-mutated breast cancer—with the majority of them having triple-negative breast cancer. Importantly, everyone with an indication for standard systemic treatment went on to receive it after surgery. Impressively, over half of the patients had a pathologic complete response to talazoparib alone. However, while non-hematologic toxicity was mild, close to half of patients required transfusions for anemia. Of note, the BrighTNess trial indicated PARP-inhibitors may not provide any incremental benefit to cytotoxic chemo—a question this study can’t answer. So for now we remain in the dark on whether single-agent targeted therapy could replace systemic therapy altogether.
TBL: The PARP-inhibitor talazoparib confers a >50% pathologic complete response rate when given as monotherapy in women with early-stage, BRCA-mutated breast cancer. | Litton, J Clin Oncol 2019


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