As reported in The Lancet by Fizazi et al, the final overall survival analysis in the homologous recombination repair (HRR)-deficient metastatic castration-resistant prostate cancer (CRPC) cohort of the phase III TALAPRO-2 trial showed a significant benefit with the addition of talazoparib to enzalutamide.
The primary analysis in this cohort showed that talazoparib plus enzalutamide significantly improved radiographic progression–free survival vs placebo plus enzalutamide in patients with HRR-deficient metastatic CRPC.
Study Details
In the double-blind trial, 399 patients with HRR-deficient disease who had received no prior life-prolonging therapy for CRPC were randomly assigned between December 2018 and January 2022 to receive talazoparib plus enzalutamide (n = 200) or placebo plus enzalutamide (n = 199). Patients received ongoing androgen-deprivation therapy. Overall survival was a key secondary endpoint.
Key Findings
At a median follow-up of 44.2 months (interquartile range = 36.0–50.8 months), median overall survival was 45.1 months (95% confidence interval [CI] = 35.4 months to not reached) in the combination group vs 31.1 months (95% CI = 27.3–35.4 months) in the control group (hazard ratio [HR] = 0.62, 95% CI = 0.48–0.81, P = .0005). Rates at 2 and 4 years were 77% vs 65% and 48% vs 28%.
Among 155 patients with BRCA1/2 alterations, median overall survival was not reached in the combination group vs 28.5 months in the control group (HR = 0.50, 95% CI = 0.32–0.78, P = .0017); 4-year overall survival rates were 53% vs 23%. Among 244 patients without BRCA1/2 alterations, median overall survival was 42.4 vs 32.6 months (HR = 0.73, 95% CI = 0.52–1.02, P = .066); 4-year rates were 46% vs 23%.
Karim Fizazi, MD
Updated radiographic progression–free survival results showed medians of 30.7 vs 12.3 months (HR = 0.47, 95% CI = 0.36–0.61, P < .0001).
No new safety signals were identified. Overall, grade ≥ 3 treatment-related adverse events occurred in 59% of the combination group vs 14% of the control group. Serious treatment-related adverse events occurred in 16% vs < 1% of patients. Grade 5 adverse events occurred in 3% of patients in each group.
The investigators concluded: “Talazoparib plus enzalutamide resulted in statistically significant and clinically meaningful improvement in survival versus enzalutamide plus placebo, further supporting this combination as a standard of care in HRR-deficient metastatic castration-resistant prostate cancer.”
Karim Fizazi, MD, of Institut Gustave Roussy, University of Paris–Saclay, Villejuif, and Neeraj Agarwal, MD, of Huntsman Cancer Institute, University of Utah, Salt Lake City, are the corresponding authors for The Lancet article.
Disclosure: The study was funded by Pfizer. For full disclosures of all study authors, visit thelancet.com.
