Definitive bladder/pelvic radiation after enfortumab vedotin–pembrolizumab for advanced urothelial carcinoma.

Abstract

e16589 Background: Treatment with enfortumab vedotin and pembrolizumab (EV-P) is highly effective in patients (pts) with advanced urothelial carcinoma. The optimal local therapy for residual or oligoprogressive disease in the bladder after EV-P remains to be defined. Radiation (RT) to the bladder is highly effective in appropriately selected pts with muscle-invasive bladder cancer. Here, we report outcomes for pts receiving definitive bladder or pelvic RT after EV-P. Methods: A retrospective institutional database of pts treated with EV-P (n = 256) was reviewed to identify pts who received bladder or pelvic RT. RT-intent (consolidative, oligoprogressive, palliative) was coded. Investigator-assessed local control (LC), defined by recurrence at a RT-treated site, progression free survival (PFS), and overall survival (OS) were estimated from RT start. Treatment-related toxicity was retrospectively graded using CTCAE both acutely (within 3m of RT) and at 6-month intervals. Results: 36 pts received EV-P and RT to the bladder/pelvis. 24 were treated with definitive intent (for oligoprogression on/after EV-P or to consolidate non-growing residual disease). 7 were excluded from further analysis for RT given before EV-P, after intervening therapy, or > 1 year after EV-P. For the remaining 17 pts, 10 were treated for oligoprogression and 7 to consolidate residual disease. At diagnosis, 5 had M1b disease, 7 were M1a, 4 were N+M0, and 1 had N0M0 MIBC. Median follow-up was 11.7m. The median total duration of EV-P treatment was 4.1 months. All pts held EV during RT. RT was delivered to the bladder (n = 12, 4 with nodal coverage) or pelvic LNs alone (n = 5 patients); 7/17 received concurrent chemotherapy (all gemcitabine). After RT, 7/17 continued EV and/or P. LC at 12 and 24 months was 75%. 4/17 (24%) had local failure in the RT field at any time. After RT, median LC, PFS, and OS were 32.1 (95% CI NR-NR), 8.1 (95%CI 3.9-NR) and not reached (NR) (95%CI 11.9-NR) months. Median LC, PFS, and OS were not met for the consolidation patients and were 32.1, 3.9 and 11.9 months for oligoprogression pts. There were no Grade 3+ GU and 1 grade 3+ GI toxicities (a colo-vesical fistula in the context of disease progression with colonic invasion). Conclusions: Definitive bladder-pelvic RT after EV-P was well-tolerated with promising disease control, particularly in those patients receiving RT for residual non-progressing disease. Clinical outcomes and follow-up summary. Cohort Local Control Progression-Free Overall Survival All Patients 32.1 [NR to NR] 8.1 [3.9 to NR] NR [11.9 to NR] Consolidative NR [NR to NR] NR [NR to NR] NR [NR to NR] Oligoprogression 32.1 [NR to NR] 3.9 [2.2 to NR] 11.9 [8.4 to NR] NR: Not Reached; Values are Median [95% Confidence Interval] in months.