Talazoparib (TALA) plus enzalutamide (ENZA) in metastatic castration-resistant prostate cancer (mCRPC): Safety analyses from the randomized, placebo (PBO)-controlled, phase 3 TALAPRO-2 study.

Abstract

5053 Background: The phase 3 TALAPRO-2 study demonstrated a clinically meaningful and statistically significant improvement in radiographic progression-free survival for 1st-line TALA + ENZA versus PBO + ENZA in men with mCRPC, unselected for homologous recombination repair gene alterations (all-comers population). Here, we detail the safety profile of TALA + ENZA. Methods: In this double-blind, randomized, PBO-controlled trial, men received TALA 0.5 mg or PBO, plus ENZA 160 mg once daily (QD). Patient (pts) were ≥18 yrs of age, had Eastern Cooperative Oncology Group performance status ≤1, were receiving ongoing androgen deprivation therapy, and had no prior systemic therapy for mCRPC. Treatment-emergent adverse events (TEAEs) were evaluated: type, severity, timing, and associated dose modifications/discontinuations. Results: The all-comers safety population included 398 pts in the TALA + ENZA arm. Data cutoff was August 16, 2022. The median treatment duration of TALA was 19.8 months. All-cause any-grade TEAEs were observed in 98.5% of pts. Overall, 19.1% of pts discontinued TALA due to TEAEs. The 3 most common hematologic all-cause TEAEs and associated dose modifications are reported. To ensure optimal dosing of TALA at the individual level, the protocol did not require dose modification of TALA until anemia was grade (G) ≥3. Median time to onset of first G≥3 anemia was 3.3 months. At study entry, 49.0% had G1–2 anemia. 43.2% had anemia leading to dose reduction (with or without transfusion) and 8.3% discontinued TALA due to anemia. Despite dose reduction, the relative dose intensity of talazoparib remained >80% (approx. 0.4 mg/day). The 3 most common nonhematologic TEAEs were fatigue (33.7%; 4.0% G3), back pain (22.1%; 2.5% G3), and decreased appetite (21.6%; 1.3% G3). Conclusions: TALA 0.5 mg QD + ENZA 160 mg QD was generally manageable, with dose modifications of TALA and/or standard supportive care. Anemia was the most common TEAE and led to discontinuation of TALA in 8.3% of pts. G≥3 hematologic AEs typically occurred within 6 months of starting therapy and resolved in <1 month. A detailed understanding of the onset, duration, and severity of AEs, as well as the impact of dose adjustments in the TALAPRO-2 study, will optimize the management of pts receiving TALA + ENZA for mCRPC. Clinical trial information: NCT03395197 . [Table: see text]