Talazoparib and enzalutamide improve survival in metastatic castration-resistant prostate cancer

1. Progression-free survival and overall survival were significantly greater in the combination therapy group compared to enzalutamide alone.

2. Anemia and neutropenia were more common with talazoparib compared to enzalutamide alone.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Metastatic castration-resistant prostate cancer (mCRPC) is difficult to treat, with existing therapies offering limited benefit. Previous studies have shown that adding talazoparib to enzalutamide may improve survival, though further research with longer follow-up is needed. This randomized controlled trial aimed to evaluate the efficacy and safety of talazoparib plus enzalutamide compared to enzalutamide alone in mCRPC patients. The primary outcome was progression-free survival (PFS), while key secondary outcomes were overall survival and safety profile of the medications. According to study results, the combination therapy significantly improved PFS and overall survival compared to enzalutamide alone. However, the combination therapy group reported greater rates of anemia and neutropenia. Although this study was well done, it was limited by a relatively lower survival benefit in the select patients, which may affect generalizability.

Click to read the study in The Lancet

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In-depth [randomized controlled trial]: Between Jan 7, 2019, and Sept 17, 2020, 993 patients were assessed for eligibility across 200 centers in 26 countries. Included were patients ≥ 18 years with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer and no prior life-prolonging treatment for castration-resistant disease. Altogether, 805 patients (402 in enzalutamide plus talazoparib and 402 in enzalutamide only) were included in the final analysis. The primary outcome of PFS was significantly higher in the combination therapy group compared to enzalutamide only (33.1 months vs. 19.5 months, hazard ratio [HR] 0.80, p<0.0001). The secondary outcome of overall survival was also improved in talazoparib (45.8 months vs. 37.0 months, p<0.016). Grade 3 or greater anemia (49% vs. 4%) and neutropenia (19% vs. 1%) were more common among the combination therapy group compared to enzalutamide alone, respectively. Findings from this study suggest that talazoparib plus enzalutamide improves survival in patients with metastatic castration-resistant prostate cancer.

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