The indication is, more precisely, for patients with deleterious or suspected deleterious germline BRCA-mutated, HER2‑negative locally advanced or metastatic breast cancer. The recommended daily dose of talazoparib is 1 mg.
Eligible patients should have been previously treated with an anthracycline and/or a taxane in the (neo)adjuvant setting (unless they were not suitable for those treatments). Also, patients with hormone receptor-positive (HR+) breast cancer should have been treated with a prior endocrine-based therapy (unless not suitable).
The European approval follows the medicine's approval by the US Food and Drug Administration in October 2018.
The new approval was based on safety and efficacy results from the EMBRACA trial, the largest phase 3 study of a PARP inhibitor in this setting.
Median progression-free survival (PFS) was 8.6 and 5.6 months in the talazoparib and chemotherapy groups, respectively (hazard ratio, 0.54; 95% confidence interval, 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). Overall survival data are not yet mature.
The objective response rate was roughly double in the talazoparib group compared with that of the chemotherapy group (62.6% vs 27.2%; P < .001). Patient-reported outcomes also favored talazoparib.
"This improvement in outcomes for patients treated with [talazoparib] reinforces the increasingly key role of genetic testing in treatment decision-making for patients with locally advanced or metastatic breast cancer," said Johannes Ettl, MD, Klinikum rechts der Isar, Technical University of Munich, Germany, in a company press statement. He is also an EMBRACA investigator.
All patients in the trial were required to have a known deleterious or suspected deleterious germline BRCA mutation. The study results were published online in August 2018 in the New England Journal of Medicine.
Enrolled participants had to 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.
Based on pooled data from patients who received 1 mg talazoparib in clinical studies for solid tumors, the most common adverse reactions (≥ 25%) were fatigue (57.1%), anemia (49.6%), nausea (44.3%), neutropenia (30.2%), thrombocytopenia (29.6%), and headache (26.5%). Grade 3 or higher adverse reactions (≥ 10%) were anemia (35.2%), neutropenia (17.4%), and thrombocytopenia (16.8%).
EMBRACA was funded by Pfizer.
Cite this: Europe OKs PARP Inhibitor Talazoparib in BRCA+ Breast Cancer - Medscape - Jun 21, 2019.