Talazoparib plus enzalutamide improves progression-free survival in metastatic prostate cancer

1. Progression-free survival was significantly higher in the talazoparib plus enzalutamide group compared to enzalutamide alone.

2. There were no treatment-related fatalities among patients in the talazoparib group.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Prostate cancer is the second most common malignancy among men. Despite existing therapies, metastatic castration-resistant prostate cancer (mCRPC) remains a major concern. Talazoparib is a potent poly (ADP-ribose) polymerase (PARP) inhibitor that may be added to enzalutamide (the current standard of care) for clinical efficacy, although little is currently known. This randomized controlled trial aimed to assess the safety and efficacy of talazoparib plus enzalutamide as first-line therapy for patients with mCRPC. The primary outcome of this study was radiographic progression-free survival (rPFS), while a key secondary outcome included the incidence of treatment-emergent adverse events. According to study results, talazoparib plus enzalutamide demonstrated significant improvements in rPFS compared to enzalutamide alone among patients with mCRPC. Although this study was well done, it was limited by a short follow-up period for overall survival data and additional long-term safety evaluation.

Click to read the study in The Lancet

Relevant Reading: Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer

In-depth [randomized-controlled trial]: Between Jan 7, 2019, and Sept 17, 2020, 991 patients were screened for eligibility across 223 hospitals, cancer centers, and medical centers in 26 countries. Included were patients with mCRPC receiving ongoing androgen deprivation therapy. Altogether, 805 patients (402 in talazoparib and 403 in placebo) were included in the final analysis. The primary outcome of rPFS improvement was higher in the talazoparib plus enzalutamide group compared to enzalutamide alone (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.51–0.78, p<0.01). The majority of adverse events were mild-to-moderate with anemia (46%, n=185) and neutropenia being most common in the talazoparib group. There were no reported deaths among talazoparib patients although 2 (<1%) passed away in the enzalutamide group. Overall, findings from this study suggest that talazoparib plus enzalutamide is a promising first-line treatment option for patients with mCRPC.

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