222 - Bi-Institutional Safety Analysis of Combining Radiotherapy and Enfortumab Vedotin in Advanced Urothelial Cancer

Y. S. Soni¹, D. Lock², L. K. Ballas³, L. Hwang², S. Cole⁴, A. DSouza⁵, T. Zhang⁴, A. Garant¹, D. X. Yang¹, W. Arafat⁴, and N. B. Desai¹; ¹Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, ²Department of Radiation Oncology, LAC+USC Medical Center, Los Angeles, CA, ³Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, ⁴Department of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX, ⁵Department of Hematology and Oncology, LAC+USC Medical Center, Los Angeles, CA

Purpose/Objective(s): Antibody-drug conjugates (ADCs) are increasingly utilized and are particularly changing care in advanced urothelial cancer, where enfortumab vedotin (EV) has improved progression free and overall survival. However, limited data exists on the safety of EV given in proximity to radiation therapy (XRT), challenging palliation and combinatorial trial designs. We hypothesize that overlapping toxicities are limited. Materials/

Methods: Patients with advanced urothelial cancer treated with EV and XRT at two institutions were evaluated retrospectively under IRB approval. XRT details were collected, including site (pelvis without intact bladder, pelvis with intact bladder, and extra-pelvic), dose fractionation, and temporal relationship to EV infusions (prior, concurrent within 2 weeks, after). Toxicities were graded per CTCAE v5.0, and patients who discontinued EV for toxicity were further evaluated for a potential relationship with XRT.
Results: Between January 1, 2020 and January 31, 2024, 60 patients receiving EV, with median age 71 (range 43-90) and 44/60 (73%) male, were treated with XRT over 119 courses. These included XRT to the pelvis without bladder (20%), pelvis with intact bladder (19%), and extra-pelvic fields (61%). XRT was delivered as stereotactic body radiotherapy (SBRT) in 41%, with the majority (84%) of courses lasting five fractions or fewer. XRT courses occurred prior to (53%), concurrently with (23%), and after (24%) EV treatment. Of the patients who underwent concurrent EV-XRT, EV was eventually discontinued due to toxicity in 6 (10%) patients at a median of 2 months (range 0-5) after EV-XRT, related to neuropathy (4), dermatitis (1), or pneumonitis (1). These 6 patients received a total of 7 courses of XRT, of which 2 were SBRT and 5 were conventional EBRT. Five of six patients had their drug-limiting toxicity documented prior to receiving XRT and had no change in toxicity grade when comparing one month before XRT to one month after XRT. In a single patient receiving both EV and pembrolizumab with concurrent XRT, grade 3 pneumonitis was newly observed at 1 month and outside of the XRT field (bladder). At time of analysis, EV was ongoing in 15/60 (25%), stopped for progression of disease in 32/60 (53%), or stopped for toxicity in 11/60 (18%). One (2%) patient was lost to follow-up, and one patient (2%) patient died during EV of unrelated pneumonia. No toxicities were fatal or worsened immediately following concurrent XRT.
Conclusion: XRT was not associated with increased toxicity for patients receiving EV, including for those who received XRT with EV. This data sets a baseline of expected toxicities for EV and XRT, as EV is implemented in trials of earlier urothelial cancer disease states. Abstract 222 – Table 1

Total # of patients	Total # of XRT courses	Pelvis with intact bladder courses	Pelvis without intact bladder courses	Extra-pelvic courses	XRT courses prior to EV	XRT courses concurrent with EV	XRT courses after EV
60	119	23 (19%)	24 (20%)	73 (61%)	58 (49%)	25 (32%)	27 (23%)