Clinical outcomes of enfortumab vedotin (EV) or pembrolizumab (P) interruption in metastatic urothelial carcinoma (mUC).

Abstract

e16592 Background: EV–P is a standard first-line therapy for mUC. In routine practice, one agent is frequently discontinued due to toxicity with continuation of the alternate agent as monotherapy (mono). The clinical impact remains unclear. Methods: We performed a retrospective analysis of patients (pts) with mUC on EV–P. Pts were stratified by interruption of one agent with continuation of the alternate agent as mono versus uninterrupted EV-P. Overall survival (OS) and progression-free survival (PFS) were analyzed using multivariable Cox models adjusted for age, first line EV–P, synchronous metastases, extranodal disease, treatment duration, and immune-related adverse events (irAEs). Same covariates were used for 1:1 propensity score matching. Baseline characteristics were compared using Wilcoxon rank-sum and Chi-squared tests. Results: Among 159 pts, 36 (23%) interrupted treatment and continued mono, while 123 (77%) received uninterrupted EV-P combination. Baseline characteristics were comparable, including age (74 vs 72 years, p=0.35), first-line use (58.3% vs 56.9%, p=0.88), and extranodal metastases (38.9% vs 36.6%, p=0.80). Median follow-up was 9.5 months (IQR 5–18). irAEs were more frequent in the interruption group (72.2% vs 29.5%, p<0.001). Median treatment duration was longer with interruption (8.6 vs 3.8 months, p<0.001). Among the interrupted cohort, 53% continued P and 47% continued EV. In propensity-matched analysis, interruption was associated with improved PFS (HR 0.32, 95% CI 0.25–0.70, p=0.0026) and OS (HR 0.24, 95% CI 0.09–0.66, p=0.03). Among the interrupted cohort, continuation of P had higher PFS (HR 0.14, p=0.003) and OS (HR 0.28, p=0.01) than continuation of EV monotherapy. Conclusions: In this cohort, discontinuation of one EV–P component with continuation of the other agent as mono was associated with improved survival versus uninterrupted combination. Toxicity-guided treatment de-escalation may achieve durable disease control in selected pts. Patient characteristics and treatment outcomes. Variable Interrupted EV or P (N=36) No interruption in EV-P (N=123) P value Baseline demographic characteristics Age at Tx initiation 74.00 (65.75, 80.25) 72.00 (64.00, 77.50) 0.350 Sex 0.623 - Female 25.0% (9) 21.1% (26) - Male 75.0% (27) 78.9% (97) Duration of treatment 8.60 (5.33, 14.98) 3.83 (1.60, 8.32) <0.001 M stage Tx initiation 0.379 No distant metastases (M0) 16.7% (6) 23.6% (29) Metastatic disease present (M1) 83.3% (30) 76.4% (94) Treatment characteristics and discontinuation patterns Adverse events from ICI 72.2% (26) 29.5% (36) <0.001 Pembro discontinuation due to adverse event 51.4% (18) _ Pembro discontinued due to progression 11.4% (4) 27.9% (34) 0.075 Adverse events from EV 72.2%(26) 41.8% (51) 0.001 EV discontinuation due to adverse event 42.9% (15) _ EV discontinued due to progression 34.3% (12) 29.5% (36) 0.739