Clinical outcomes of metastatic urothelial carcinoma patients discontinuing enfortumab vedotin due to toxicity and/or clinical response.

Abstract

719 Background: Enfortumab vedotin (EV) monotherapy and its combination with pembrolizumab (EV/P) are established treatments for metastatic urothelial carcinoma (mUC). In clinical practice, patients who discontinue EV after achieving a complete or partial response (CR/PR), or to avoid excessive toxicity, may experience durable response. However, the treatment-free interval (TFI) after stopping EV has not been previously characterized. Methods: We retrospectively analyzed mUC pts treated with EV or EV/P at our institution. Pts receiving neoadjuvant EV/P for locally advanced disease or fewer than 2 cycles of EV or EV/P were excluded. The primary endpoint was TFI among pts who discontinued EV (with or without continuing pembrolizumab in EV/P pts) for > 8 consecutive weeks due to toxicity or CR/PR. Continuous variables were summarized using means, medians and ranges while categorical variables with frequencies and proportions. TFI was evaluated using cumulative incidence curves and Fine Gray models with treatment re-initiation and death as two competing events. Results: Among 146 pts (median age 72 years; 80% men), 78 received EV and 68 received EV/P. Seventy-two pts (49.3%) discontinued EV for >8 weeks due to toxicity and/or CR/PR (32 EV; 40 EV/P). Median treatment duration before discontinuing was 6.1 months (range, 1.4-15.4) with EV and 4.6 months (range, 1- 22) with EV/P. At 1 year after stopping EV, 43.75% of EV and 66.98% of EV/P patients remained alive and treatment-free (Table). Duration of EV prior to stopping did not predict TFI (EV: HR 1.02, p = 0.77; EV/P: HR 0.91, p = 0.33). Patients achieving CR had significantly longer TFI than those with PR (HR 5.06, p = 0.01). Among 22 patients who reinitiated EV at progression, 24% achieved PR, 33% stable disease, and 43% progressed. Conclusions: Nearly half of mUC patients stopping EV due to toxicity or clinical response remained treatment-free and alive at 1 year. Duration of prior EV exposure did not influence TFI, but achieving CR was associated with significantly prolonged TFI. Re-treatment with EV upon progression yielded disease control in over half of patients. Cumulative incidence at 1 year of stopping EV. EV Group (n = 32) EV/P Group (n=40) Alive and treatment-free 43.75% 66.98% Incidence of restarting any treatment 31.25% 24.66% Incidence of death 25% 8.36%