Site Editor
Sandy Srinivas, MD
Sandy Srinivas, MD
Posted: Wednesday, June 21, 2023
On June 20, the U.S. Food and Drug Administration (FDA) approved talazoparib (Talzenna) with enzalutamide (Xtandi) for treatment of patients with homologous recombination repair (HRR)-mutated metastatic castration-resistant prostate cancer. The PARP inhibitor talazoparib is also indicated for treatment of adults with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer. The androgen receptor inhibitor enzalutamide is indicated for treatment of patients with castration-resistant or metastatic castration-sensitive prostate cancers.
This approval is based on the results of the phase III TALAPRO-2 trial, which compared enzalutamide at 160 mg daily plus either talazoparib at 0.5 mg (n = 200) or placebo daily (n = 199) in patients with HRR-mutated metastatic castration-resistant prostate cancer. Patients were required to have a prior orchiectomy and, if not performed, received gonadotropin-releasing hormone analogs. HRR genes (ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C) were assessed prospectively using tumor tissue and/or circulating tumor DNA–based next-generation sequencing assays.
A statistically significant improvement in radiographic progression–free survival for talazoparib plus enzalutamide compared with placebo plus enzalutamide was observed in the HRR-mutated population, with a median that was not reached versus 13.8 months (hazard ratio = 0.45; 95% confidence interval [CI] = 0.33–0.61; P < .0001). In an exploratory analysis by BRCA mutation status, the hazard ratio for radiographic progression–free survival in patients with BRCA-mutated metastatic castration-resistant prostate cancer (n =1 55) was 0.20 (95% CI = 0.11–0.36), and in patients with non–BRCA-mutated, HRR-mutated metastatic castration-resistant prostate cancer, it was 0.72 (95% CI = 0.49–1.07).
The most common adverse reactions (≥ 10%) with the combination therapy, including laboratory abnormalities, were decreased hemoglobin, decreased neutrophils, decreased lymphocytes, fatigue, decreased platelets, decreased calcium, nausea, decreased appetite, decreased sodium, decreased phosphate, fractures, decreased magnesium, dizziness, increased bilirubin, decreased potassium, and dysgeusia. Among all patients with metastatic castration-resistant prostate cancer treated with talazoparib plus enzalutamide in TALAPRO-2, 39% required a blood transfusion, including 22% who required multiple transfusions.
U.S. Food and Drug Administration
