FDA approves talazoparib with enzalutamide for HRR gene-mutated metastatic castration-resistant prostate cancer
Regulatory approval: On June 20, 2023, the FDA approved talazoparib (Talzenna) in combination with enzalutamide for patients with homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer (mCRPC). Approval was supported by the randomized, double-blind, placebo-controlled TALAPRO-2 trial, which showed a statistically significant improvement in radiographic progression-free survival (rPFS) for talazoparib plus enzalutamide versus placebo plus enzalutamide.
FDA approval (June 20, 2023)
The US Food and Drug Administration (FDA) approved talazoparib (Talzenna; Pfizer) in combination with enzalutamide for homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer (mCRPC).
Supporting evidence: TALAPRO-2 (NCT03395197)
Efficacy was evaluated in TALAPRO-2, a randomized, double-blind, placebo-controlled, multi-cohort trial enrolling 399 patients with HRR gene–mutated mCRPC. Patients were randomized 1:1 to enzalutamide 160 mg daily plus talazoparib 0.5 mg daily or enzalutamide plus placebo. Prior systemic therapy for mCRPC was excluded; prior CYP17 inhibitors or docetaxel for mCSPC was permitted. HRR alterations (including ATM, ATR, BRCA1/2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C) were assessed prospectively using tumor tissue and/or ctDNA NGS.
The primary endpoint was rPFS by blinded independent central review. Median rPFS was not reached with talazoparib/enzalutamide vs 13.8 months with placebo/enzalutamide (HR 0.45; 95% CI 0.33–0.61; p<0.0001). In an exploratory analysis, rPFS HR was 0.20 (95% CI 0.11–0.36) in BRCA-mutated disease (n=155) and 0.72 (95% CI 0.49–1.07) in non-BRCA HRR-mutated disease.
Safety highlights
Common adverse reactions (≥10%; including laboratory abnormalities) included cytopenias (e.g., decreased hemoglobin), fatigue, nausea, decreased appetite, fractures, and electrolyte abnormalities. Among all mCRPC patients treated with talazoparib/enzalutamide in TALAPRO-2 (n=511), 39% required a blood transfusion (22% multiple), and 2 patients were diagnosed with MDS/AML.
Dosing in label
Recommended doses: talazoparib 0.5 mg orally once daily with enzalutamide 160 mg once daily until progression or unacceptable toxicity, with concurrent GnRH analog unless bilateral orchiectomy.
The application received priority review.