Pre-progression discontinuation and off-treatment progression-free interval after enfortumab vedotin–based therapy among patients with clinical benefit in advanced urothelial carcinoma: A single-institution experience.

e16593 Background: In routine practice, enfortumab vedotin (EV) ± pembrolizumab (EVP) may be discontinued before progression due to toxicity, cost, or patient preference. We quantified (1) the frequency and reasons for pre-progression discontinuation (PPD) among patients with clinical benefit and (2) off-treatment progression-free interval (OT-PFI) after stopping, including descriptive EV vs EVP comparisons where feasible. Methods: Single-center retrospective cohort of advanced urothelial carcinoma treated with EV or EVP. Clinical benefit (CB) was best response CR/PR/SD on the EV/EVP-containing line. PPD was any recorded non-progression discontinuation reason (toxicity, cost, patient decision, including EV-component discontinuation within EVP). OT-PFI was measured from EV/EVP end date to PD or death, censored at last follow-up (Kaplan–Meier). EV vs EVP results are descriptive. Results: Among 101 EV/EVP-treated patients, 81 achieved CB (EV 39; EVP 42). PPD occurred in 31/81 (38.3%), higher in EVP than EV (20/42 47.6% vs 11/39 28.2%). PPD reasons (as % of CB population) were toxicity 17/81 (21.0%; neuropathy 11, skin toxicity 3, pneumonitis 2, general weakness 1; EVP included EV-component discontinuation n = 3), cost 6/81 (7.4%), and patient decision 8/81 (9.9%). Deep response (CR) was more frequent in PPD vs ongoing/until PD (6/31 19.4% vs 2/50 4.0%). Median cycles (available data) were lower in PPD vs ongoing/until PD: overall 5 (n = 16) vs 6 (n = 33); EV 3 (n = 7) vs 5 (n = 21); EVP 5 (n = 9) vs 7 (n = 12). Subsequent systemic therapy after the EV/EVP line was initiated in 1/31 (3.2%) in PPD vs 21/50 (42.0%) in ongoing/until PD (EV: 1/11 vs 13/28; EVP: 0/20 vs 8/22). OT-PFI was evaluable in 16/31 PPD patients with documented end dates (EV 7; EVP 9; 2 events). Six-month OT-PFI was 59.3% overall (EV 75.0%; EVP 66.7%); median OT-PFI was not reached. Conclusions: In real-world practice, more than one-third of CB patients had recorded discontinuation of EV-based therapy before progression, most commonly due to toxicity. In the evaluable subset, OT-PFI after stopping was frequently prolonged, suggesting that a drug-free interval may be feasible in selected responders. EV vs EVP comparisons are exploratory due to limited events and incomplete stop-date documentation.