Adding talazoparib to first-line treatment with enzalutamide improves radiographic progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations, according to data presented at the ASCO Annual Meeting 2023.
The data, from the phase 3 TALAPRO-2 trial (ClinicalTrials.gov Identifier: NCT03395197), were presented by Karim Fizazi, MD, of Institut Gustave Roussy in Villejuif, France.
Dr Fizazi reported findings from 399 patients with HRR-deficient mCRPC who were randomly assigned to receive first-line treatment with talazoparib at 0.5 mg daily (n=200) or placebo (n=199) in addition to enzalutamide at 160 mg daily.
Patients in the talazoparib arm had a 55% lower risk of radiographic progression or death than patients in the placebo arm. The median rPFS was not reached in the talazoparib arm and was 13.8 months in the placebo arm (hazard ratio [HR], 0.45; 95% CI, 0.33-0.61; P <.001).
Among patients with BRCA alterations, talazoparib was associated with an 80% lower risk of radiographic progression or death (HR, 0.20; 95% CI, 0.11-0.36; P <.001).
Patients in the talazoparib arm also had a 59% lower risk of prostate-specific antigen (PSA) progression. The median time to PSA progression was 28.6 months in the talazoparib arm and 11.1 months in the placebo arm (HR, 0.41; 95% CI, 0.30-0.57; P <.0001).
In addition, patients in the talazoparib arm had a significantly longer time to receipt of cytotoxic chemotherapy (HR, 0.46; 95% CI, 0.31-0.70; P =.0001) and a longer second progression-free survival (HR, 0.57; 95% CI, 0.39-0.85; P =.0045).
Although the overall survival (OS) data are immature, there was a favorable trend toward improved OS in the talazoparib arm. The median OS was not reached in the talazoparib arm and was 33.7 months in the placebo arm (HR, 0.69; 95% CI, 0.46-1.03; P =.068).
The median time to definitive clinically meaningful deterioration in global health status/quality of life was significantly longer in the talazoparib arm than in the placebo arm — 27.1 months and 19.3 months, respectively (HR, 0.69; 95% CI 0.49-0.97; P =.032).
Toxicity was generally manageable and consistent with the known safety profiles of talazoparib and enzalutamide. A greater proportion of patients in the talazoparib arm than in the placebo arm experienced grade 3-4 treatment-emergent adverse events (TEAEs, 66.2% vs 37.2%).
The most common TEAEs leading to dose reductions in the talazoparib arm were anemia (42.9%), neutropenia (15.2%), and thrombocytopenia (5.6%). Four percent of patients discontinued talazoparib due to anemia.
Based on these results, Dr Fizazi concluded that talazoparib in combination with enzalutamide, if approved, should become a standard first-line treatment for patients with mCRPC and HRR gene alterations.
Disclosures: This study was supported by Pfizer Inc. Astellas Pharma Inc. provided enzalutamide. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Fizazi K, Azad A, Matsubara N, et al. TALAPRO-2: Phase 3 study of talazoparib (TALA) + enzalutamide (ENZA) versus placebo (PBO) + enzalutamide as first-line (1L) treatment of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) gene alterations. ASCO 2023. June 2-6, 2023. Abstract 5004.