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
Abdullah et al. (Thu,) studied this question.