Talazoparib With Enzalutamide Approved for HRR Gene-Mutated Metastatic Castration-Resistant Prostate Cancer

The US Food and Drug Administration (FDA) has approved talazoparib in combination with enzalutamide for the treatment of patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer.

This approval is based on results from the double-blind, multi-cohort, phase 3 TALAPRO-2 trial, which enrolled 399 patients with HRR gene-mutated metastatic castration-resistant prostate cancer and randomized them on a 1-to-1 basis to receive 160 mg enzalutamide daily plus either 0.5 mg talazoparib or placebo daily. Patients had not received prior systemic therapy for castration-resistant prostate cancer.

There was a statistically significant improvement of radiographic progression-free survival (rPFS) among those patients treated with talazoparib with enzalutamide compared to the placebo. The median rPFS in the talazoparib arm was not reached, vs 13.8 months in the placebo arm (hazard ratio [HR], 0.45; 95% confidence interval, 0.33 to 0.61; P < .0001). The HR for rPFS among patients with BRCA-mutated disease (n = 155) was 0.20, compared to an HR of 0.72 among patients with non-BRCA-mutated, HRR gene-mutated disease.

The most common adverse events which occurred in ≥10% of patients were decreased hemoglobin, decreased neutrophils, decreased lymphocytes, fatigue, decreased platelets, decreased calcium, nausea, decreased appetite, decreased sodium, decreased potassium, and dysgeusia. Of all the patients treated with talazoparib with enzalutamide (n = 511), 39% required blood transfusions, with 22% requiring multiple transfusions. There were 2 patients who were diagnosed with myelodysplastic syndrome/acute myeloid leukemia.

The recommended dose with this approval is 0.5 mg talazoparib in combination with 160 mg enzalutamide, both taken orally once a day, until disease progression or unacceptable toxicity. If patients have not undergone a bilateral orchiectomy, a gonadotropin-releasing hormone analog should be given concurrently with this regimen.

Source:

FDA approves talazoparib with enzalutamide for HRR gene-mutated metastatic castration-resistant prostate cancer. News release. US Food and Drug Administration; June 20, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-talazoparib-enzalutamide-hrr-gene-mutated-metastatic-castration-resistant-prostate