Efficacy and safety of enzalutamide (ENZA) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) and cardiometabolic comorbidities (CMDs) and/or related concomitant medications (meds): ARCHES post hoc.

5092 Background: In ARCHES, ENZA improved radiographic progression-free survival (rPFS; primary: data cutoff, Oct 14, 2018) and overall survival (OS; prespecified secondary: data cutoff, May 28, 2021; 5-yr follow-up; data cutoff: Jul 31, 2024) vs placebo (PBO) in mHSPC. Our objective was to evaluate efficacy/safety of ENZA in pts with CMDs on related concomitant meds. Methods: We examined two groups: 1) full CMD (fCMD): pts with CMDs or on concomitant CMD meds; 2) confirmed CMD (cCMD): pts on CMD-related meds + confirmed CMD diagnosis, validated by medical history captured in concomitant med domain. CMDs included hypertension, cardiac disorders, dyslipidemia, diabetes mellitus. Related concomitant meds were diabetes meds, vasoprotectives, cardiac meds, lipid-modifying agents, antithrombotics, antihypertensives. Primary endpoint: rPFS (fCMD population; data cutoff: Oct 14, 2018). Other endpoints: OS, safety (fCMD population; data cutoff: May 28, 2021). Kaplan–Meier used for time-to-event analysis, with treatment (tx)-group comparisons assessed by stratified log-rank test and hazard ratios (HRs) relative to PBO using Cox proportional hazard models. Sensitivity analysis with cCMD population evaluated rPFS and OS, with OS adjusted for crossover with rank-preserved structure failure time model. Results: Of 1150 pts, 938 (82%) were categorized as fCMD and 756 (66%) as cCMD. In the fCMD group, ENZA showed an association with improved rPFS and OS, with similar results for all sensitivity analyses (Table). Similar results also seen in all concomitant med subgroups. At 2021 data cutoff, median tx duration was 41 mo in the ENZA arm, 14 mo in the PBO arm. Tx-emergent adverse event (TEAE) rates (per 100 pt-yr) were similar with ENZA (313.8) and PBO (468.0). TEAEs of special interest rates (per 100 pt-yr) with ENZA vs PBO: fatigue (14.4 vs 18.0); falls (6.2 vs 2.6); fractures (7.3 vs 5.4); select cardiovascular events (2.5 vs 1.6); convulsions (0.2 vs 0.5). No new safety signals were identified. Conclusions: Similar to the overall mHSPC study population, ENZA was efficacious and tolerable in pts with CMD. Optimizing CMD may further enhance outcomes for pts with mHSPC, but ENZA remains a front-line option for all mHSPC pt subgroups. Clinical trial information: NCT02677896 . ENZA, n (%) ENZA, median (mo) (95% CI) PBO a , n (%) PBO a , median(mo) (95% CI) HR (95% CI) a Nominal P value fCMD n = 468 n = 470 rPFS 73 (16) NE (NE–NE) 159 (34) 19.5 (16.6–NE) 0.39 (0.29–0.51) <0.0001 OS 123 (26) NE (NE–NE) 169 (36) NE (49.7–NE) 0.62 (0.49–0.78) <0.001 Crossover adjusted OS b 123 (26) NE (NE–NE) 169 (36) 49.7 (44.5–NE) 0.56 (0.43–0.69) <0.001 cCMD n = 377 n = 379 rPFS b 59 (16) NE (NE–NE) 126 (33%) 19.5 (16.6–NE) 0.41 (0.30–0.56) <0.0001 OS b 98 (26) NE (NE–NE) 137 (36)