Talazoparib and Enzalutamide Combo Shows Improved Survival in Metastatic Prostate Cancer Patients

Strategic Insights -

The combination of talazoparib (Talzenna) and enzalutamide (Xtandi) has been found to improve overall survival (OS) in patients with metastatic castration-resistant prostate cancer (CRPC), according to a press release on findings from the phase 3 TALAPRO-2 trial. The experimental combination significantly improved OS compared to enzalutamide monotherapy in both cohorts of patients, including those with metastatic CRPC harboring homologous recombination repair (HRR) mutations. Final analysis findings highlighted clinically meaningful radiographic progression-free survival (rPFS) improvements with the combination therapy across both cohorts, which were consistent with data from the primary analysis previously reported in February 2023.

Key Takeaways:

  • The combination of talazoparib and enzalutamide improved overall survival (OS) in patients with metastatic castration-resistant prostate cancer (CRPC), regardless of mutation status.
  • The median radiographic progression-free survival (rPFS) was not reached with talazoparib/enzalutamide vs 21.9 months with enzalutamide alone (HR, 0.63; 95% CI, 0.51-0.78; P.
  • The combination therapy also showed a statistically significant OS improvement among all-comers in cohort 1 and patients in cohort 2, which included those with metastatic CRPC harboring HRR mutations.
  • The safety profile of talazoparib plus enzalutamide in the TALAPRO-2 trial was comparable with prior reports of each individual agent.
  • The FDA previously approved talazoparib/enzalutamide for patients with HRR-mutated metastatic CRPC.
  • Common adverse effects in the trial included decreased neutrophil counts, decreased lymphocytes, fatigue, decreased calcium, nausea, decreased appetite, and decreased sodium.

Statistics:

  • Median rPFS not reached with talazoparib/enzalutamide vs 21.9 months with enzalutamide alone (HR, 0.63; 95% CI, 0.51-0.78; P.
  • Median OS not reached with talazoparib/enzalutamide vs enzalutamide alone in cohort 1.
  • 1035 patients with metastatic CRPC were assigned to receive enzalutamide at 160 mg per day with or without talazoparib at 0.5 mg per day.
  • 805 patients were all-comers and 399 patients had HRR-mutated disease.
  • The study population included patients 18 years and older with histologically or cytologically confirmed adenocarcinoma of the prostate without small cell or signet cell features and asymptomatic or mildly symptomatic metastatic CRPC.

Sources:

  • 1. Pfizer. (2024). Press release: Pfizer’s Talzenna (talazoparib) in combination with Xtandi (enzalutamide) showed statistically significant and clinically meaningful overall survival improvement in the phase 3 TALAPRO-2 trial in patients with metastatic castration-resistant prostate cancer.
  • 2. Pfizer. (2023). Press release: Pfizer announces positive top-line results from the phase 3 TALAPRO-2 trial evaluating the combination of Talzenna (talazoparib) and Xtandi (enzalutamide) in patients with metastatic castration-resistant prostate cancer.
  • 3. Pfizer. (2023). Press release: Pfizer receives FDA approval for Talzenna (talazoparib) in combination with Xtandi (enzalutamide) for patients with homologous recombination repair-mutated metastatic castration-resistant prostate cancer.
  • 4. NCT03395197. (n.d.). A Study of Talazoparib (OG-0126) in Combination With Enzalutamide (Xtandi) in Men With Metastatic Castration-Resistant Prostate Cancer (TALAPRO-2).