The US Food and Drug Administration (FDA) has approved the oral therapy talazoparib (Talzenna, Pfizer), a poly (ADP-ribose) polymerase (PARP) inhibitor, for patients with advanced BCRA-positive breast cancer.
More specifically, the indication is for patients with deleterious or suspected deleterious germline BRCA-mutated, HER2‑negative locally advanced or metastatic breast cancer.
Use must be based on an FDA-approved companion diagnostic for talazoparib.
The new approval was based on safety and efficacy results from the phase 3, open-label EMBRACA trial, which randomly assigned 431 patients (2:1) to talazoparib or physician's choice of chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine).
Estimated median progression-free survival (PFS) was 8.6 and 5.6 months in the talazoparib and chemotherapy groups, respectively (HR, 0.54; 95% CI, 0.41, 0.71; P < .0001).
PFS was the primary efficacy outcome and was assessed by blinded independent central review, according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Overall survival data are not yet mature.
The objective response rate was higher in the talazoparib than the chemotherapy group (62.6% vs 27.2%; P < .001). Patient-reported outcomes also favored talazoparib.
"I think what was really striking was that patients felt better on [talazoparib] than on chemotherapy, and the time to meaningful deterioration was significantly improved on talazoparib than on standard chemotherapy," said lead author Jennifer Litton, MD, of the University of Texas MD Anderson Cancer Center, Houston, in an email to Medscape Medical News when the study was published online in August in the New England Journal of Medicine.
All patients in the trial, which is the largest ever conducted in this setting and was supported by Pfizer, were required to have a known deleterious or suspected deleterious germline BRCA mutation. Participants also must have received three or fewer prior cytotoxic chemotherapy regimens. Furthermore, patients were required to have received treatment with an anthracycline and/or taxane (unless contraindicated) in the neoadjuvant, adjuvant, and/or metastatic treatment setting.
Hematologic grade 3-4 adverse events (mostly anemia) occurred in 55% of patients who received talazoparib and 38% of patients who received chemotherapy. However, the authors pointed out that most of these events seen with talazoparib were not associated with substantial clinical sequelae and did not result in drug discontinuation.
The most common (≥ 20%) adverse reactions of any grade were fatigue, anemia, nausea, neutropenia, headache, thrombocytopenia, vomiting, alopecia, diarrhea, and decreased appetite.
The FDA also highlighted that the prescribing information includes warnings and precautions for myelodysplastic syndrome/acute myeloid leukemia, myelosuppression, and embryo-fetal toxicity.
The FDA also approved the BRACAnalysis CDx test (Myriad Genetic Laboratories) to identify patients with breast cancer with deleterious or suspected deleterious germline BRCA mutation who are eligible for talazoparib.
The recommended daily dose of talazoparib is 1 mg.
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Cite this: FDA Approves PARP Inhibitor Talazoparib in BRCA+ Breast Cancer - Medscape - Oct 16, 2018.