Efficacy And Tolerability Of First-Line Abiraterone Plus Prednisone (Abi) Versus Enzalutamide (Enz) For Metastatic Castration-Resistant Prostate Cancer (Mcrpc) In Men >= 80 Years: A Retrospective Cohort Study.

5051 Background: ABI and ENZ are first-line treatment options for mCRPC with comparable efficacy. In men ≥ 75 years, ABI and ENZ are associated with higher rates of adverse events. For very elderly patients (pts), the efficacy and tolerability of ABI and ENZ have not been directly compared. Methods: Retrospective analysis in pts ≥ 80 years of age who received ABI or ENZ for first-line treatment of mCRPC between July 2009 and September 2016 at the BC Cancer Agency. Medical records were reviewed for clinical characteristics and outcomes including PSA response rate (PSA50) (decrease of ≥50% from baseline), time to first progression (TTP) (PSA, radiographic or clinical progression) and overall survival (OS). Results: There were 106 pts in the ABI cohort and 104 in the ENZ cohort. Baseline characteristics were well balanced including median age 85 years (IQR 83-88); median Charlson Comorbidity Index (CCI) 7 (IQR 7-8); hemoglobin (HB) < 130 in 75%; ECOG PS 0-1 in 60%; serum alkaline phosphatase (ALP)/LDH > upper limit of normal (ULN) in 32%/35% and bone/lung/liver metastasis in 86%/10%/6%. Time from start of androgen deprivation therapy to castration-resistance (TTCR) was < 12 months (m) in 16% vs 29% for ABI vs ENZ (p = 0.031). PSA50 was 43.4 % for ABI vs 77.9 % for ENZ (p < 0.001, Χ2) and median TTP was 4.7 m vs 8.0 m (HR 1.52, 95% CI 1.12-2.08). On multivariable analysis, factors associated with TTP were: treatment arm ABI vs ENZ (HR 1.76, 95% CI 1.27-2.45), ALP > ULN (HR 1.89, 95% CI 1.34-2.68), HB < 130 (HR 1.61, 95% CI 1.13-2.30), CCI > 7 (HR 1.57, 95% CI 1.13-2.19) and TTCR > 12 months (HR 1.73, 95% CI 1.18-2.55). At least one dose reduction due to toxicity was required for 7.5% of pts for ABI vs 29.8% for ENZ (P˂0.001, Χ2). For pts in the ENZ cohort who had a dose reduction, the median TTP was 11.8 m vs 6.2 m for those without (HR 0.65, 95% CI 0.40-1.08). Median OS was 13.2 m for ABI vs 18.7 m for ENZ (HR 1.20, 95% CI 0.89-1.63). Conclusions: In this very elderly cohort, the PSA50 and TTP were superior for the ENZ cohort compared to the ABI cohort despite more dose reductions in the ENZ cohort. The retrospective nature of the analysis is a limitation of this study.