Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: Safety analyses from the randomized, placebo-controlled, phase III TALAPRO-2 study

Abstract

This detailed analysis further characterizes the safety profile of talazoparib plus enzalutamide in the ongoing randomized, phase III TALAPRO-2 study in patients with metastatic castration-resistant prostate cancer (mCRPC). In both the all-comers and homologous recombination repair (HRR)-deficient populations, talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with placebo plus enzalutamide. The talazoparib plus enzalutamide safety populations in TALAPRO-2 included 398 patients from cohort 1 (all-comers, unselected for HRR gene alterations) and 198 patients from the combined HRR-deficient population (patients from the all-comers population with HRR gene alterations plus subsequently enrolled patients with HRR gene alterations; cohort 2). Patients received talazoparib 0.5mg (0.35mg, moderate renal impairment) and enzalutamide 160mg once daily. Safety analyses evaluated common treatment-emergent adverse events (TEAE), their type, severity, timing, seriousness, and relationship to study treatment. In the all-comers (n=398) and HRR-deficient populations (n=198), all-cause grade 3/4 (G3/4) TEAEs with talazoparib plus enzalutamide were reported in 71.9% and 66.2% of patients, respectively. Most common G3/4 hematologic TEAEs were anemia (46.7% and 40.9%, respectively), neutropenia (18.3% and 18.7%), and thrombocytopenia (7.3% and 7.1%). Median time to event was 3.3 and 3.3 months for G3/4 anemia, 2.3 and 2.3 months for G3/4 neutropenia, and 2.3 and 1.5 months for G3/4 thrombocytopenia. Maximum hemoglobin reduction occurred after 13 and 15 weeks of treatment. 18.8% and 10.1% of patients discontinued talazoparib. TEAEs were managed with dose interruption (62.1% and 57.6%), reduction (52.8% and 52.0%), hematologic supportive care (13.1% and 10.6%), and packed red blood cell transfusions (39.2% and 35.9%). Talazoparib plus enzalutamide had a generally manageable safety profile in patients with mCRPC within the all-comers and the HRR-deficient populations. NCT03395197.