5043 Background: The randomized, Phase 3 TALAPRO-2 trial showed improved radiographic progression-free survival (rPFS) and overall survival (OS) in pts with mCRPC treated with TALA + ENZA vs placebo + ENZA in two cohorts: unselected and homologous recombination repair (HRR)-deficient pts. Median TALA duration of treatment (DoT) was 19.7 mo (unselected) and 20.3 mo (HRR-deficient). Study protocol required dose reduction for pts with reported Grade 3 or 4 hematologic adverse events (AEs); 55% of pts in both cohorts had a TALA dose reduction due to AEs at final analysis. We analyze the impact of baseline demographics on TALA dose reductions and clinical outcomes in the TALA + ENZA arm. Methods: Pts in the TALA + ENZA arm received TALA 0.5 mg (in case of moderate renal impairment 30–59 mL/min/1.73 m 2 0.35 mg) + ENZA 160 mg PO QD. Time-to-event endpoints were summarized by the Kaplan–Meier method and compared by log-rank test. Results: In both cohorts, pts with a TALA dose reduction due to any cause (AEs and other reasons) were more likely to be older, be of Asian ethnicity, have lower bodyweight (BW), and have mild renal impairment vs pts without a TALA dose reduction (Table). Fewer pts with a TALA dose reduction than without discontinued treatment before wk 16 in the unselected (6.1% vs 20.0%) and HRR-deficient (2.7% vs 13.8%) cohorts. Median TALA DoT was longer in pts with a TALA dose reduction in the unselected cohort and similar between groups in the HRR-deficient cohort (Table). No clinically meaningful differences were observed in rPFS or OS in pts with a TALA dose reduction vs without in both cohorts (unselected: rPFS HR 0.94; 95% CI 0.70–1.25; OS HR 0.90; 95% CI 0.68–1.20; HRR-deficient: rPFS HR 0.96; 95% CI 0.64–1.44; OS HR 0.98; 95% CI 0.64–1.49; Table). Conclusions: Pts with specific baseline demographics (older, Asian ethnicity, lower BW, mild renal impairment) were more likely to have a TALA dose reduction. TALA dose reduction did not negatively impact TALA DoT or efficacy in pts who received TALA + ENZA in the TALAPRO-2 trial. Clinical trial information: NCT03395197 . Unselected with dose reduction(n=228) Unselected without dose reduction(n=170) HRR-deficient with dose reduction(n=111) HRR-deficient without dose reduction(n=87) Median age (range), y 73.0 (52–90) 70.0 (41–87) 73.0 (53–90) 68.0 (41–88) White, % 53.1 70.0 60.4 78.2 Black/African American, % 2.6 2.9 3.6 2.3 Asian, % 39.5 21.2 31.5 11.5 Median weight (range), kg 75.0 (45–169) 85.0 (59–155) 78.0 (45–118) 85.0 (60–135) Mild renal impairment (60–89 mL/min/1.73 m 2 ), % 52.2 36.5 59.5 34.5 Median TALA DoT (range), mo 23.0 (1.9–67.4) 15.2 (0.1–58.6) 20.3 (2.6–61.1) 20.8 (0.3–58.6) Median rPFS (95% CI), mo 33.1 (27.4–41.4) 33.0 (22.3–41.4) 33.1 (24.3–38.5) 30.2 (18.1–46.7) Median OS (95% CI), mo 46.9 (40–53.3) 45.1 (30.7–57.2) 41.9 (35.4–not reached NR) 48.4 (31.5–NR)
Giorgi et al. (2026) studied this question.