Description and management strategies of prespecified treatment emergent adverse events (TEAEs) amongst patients (pts) treated with 1L enfortumab vedotin (EV) + pembrolizumab (P) for la/mUC in a real-world setting.

671 Background: Based on EV-302 study results, EV+P is considered the standard of care therapy for 1L la/mUC. In EV-302, the most common Grade (G) ≥3 TEAEs of special interest for EV in the EV+P arm were skin reactions, peripheral neuropathy, and hyperglycemia. This real-world study aimed to describe prespecified G2 and G≥3 TEAEs and management strategies in pts who experienced these TEAEs during EV+P treatment for 1L la/mUC. Methods: This chart review study used the Cardinal Health OPEN oncology network in the US. Eligible adult pts had la/mUC, initiated 1L EV+P on/after 22-Oct-2023, experienced ≥1 prespecified TEAE, and had ≥6 mo of follow-up data. Prespecified TEAEs were selected due to being common with EV+P treatment and included non-hematologic TEAEs with dose modification recommendations in the USPI. TEAE management strategies were abstracted by treating physicians. Pts may have experienced ≥1 prespecified TEAE and ≥1 management strategy may have been implemented per TEAE. Results: In this cohort of pts (N=225), all of whom had ≥1 prespecified G≥2 TEAE, baseline characteristics included median (Q1–Q3) age of 69 (63–74) y, 69% male, 69% White, and 80% ECOG PS 0–1. At data cutoff, 41.8% of pts receiving 1L EV+P (n=94/225) had discontinued EV treatment, while 58.2% (n=131/225) remained on therapy. The reasons for EV discontinuations (n=94) were AE(s)/toxicity (n=38; 40.4%), disease progression (n=32; 34.0%), pt choice (n=14; 14.9%), physician decision (n=5; 5.3%), and/or death (n=4; 4.3%). Among all pts, first EV dose reductions and first delays/interruptions due to any TEAE occurred in 91 (40.4%) and 61 (27.1%) pts, respectively, with a median (Q1–Q3) time from EV initiation to dose reduction or delay/interruption of 67 (26–123) and 59 (29–106) days, respectively. Table shows rates of prespecified TEAEs and associated first dose reductions and/or delays/interruptions by TEAE/grade. Conclusions: EV dose modifications were frequently used to manage TEAEs in this real-world cohort; further data on management will be presented. Prespecified TEAEs, n (%) G2 G≥3 First EV dose reduction (G2 a / G≥3 b ) First EV dose delay/interruption (G2 a / G≥3 b ) Fatigue - c 36 (16.0) - / 13 (36.1) - / 1 (2.8) Diarrhea - c 29 (12.9) - / 7 (24.1) - / 10 (34.5) Decreased appetite - c 24 (10.7) - / 7 (29.2) - / 1 (4.2) Peripheral neuropathy 58 (25.8) 7 (3.1) 30 (51.7) / 3 (27.3) 17 (29.3) / 5 (45.5) Rash 37 (16.4) 4 (1.8) 18 (48.6) / 2 (50.0) 10 (27.0) / 2 (50.0) Hyperglycemia 34 (15.1) 4 (1.8) 8 (22.9) / 1 (16.7) 7 (20.0) / 5 (83.3) Dry skin 30 (13.3) 6 (2.7) 2 (6.5) / 0 3 (9.7) / 0 Pruritus 13 (5.8) 6 (2.7) 1 (7.7) / 1 (14.3) 4 (30.8) / 2 (28.6) Pneumonitis 6 (2.7) 3 (1.3) 1 (16.7) / 1 (33.3) 1 (16.7) / 1 (33.3) a % based on pts with G2 prespecified TEAEs. b % based on pts with G≥3 prespecified TEAEs; c Only prespecified as G≥3 TEAE.