Clinical outcomes of metastatic urothelial carcinoma pts discontinuing enfortumab vedotin.

Abstract

e16574 Background: Enfortumab vedotin (EV) monotherapy and its combination with pembrolizumab (EV/P) are established treatment options in metastatic urothelial carcinoma (mUC). However, significant toxicities associated with EV and EV/P often lead to treatment discontinuation. Despite this, some patients maintain disease control beyond discontinuation, suggesting the potential for treatment re-challenge. This study aimed to evaluate pts who discontinued EV for >8 weeks to examine the time to disease progression after discontinuation and the efficacy of EV re-challenge. Methods: This retrospective study analyzed clinical data from 86 pts who received either EV or EV/P for mUC in either the first or subsequent lines of therapy between January 2018 and June 2024.Descriptive statistics were employed for data analysis, and the Kaplan-Meier estimator was used to calculate survival probabilities. The interquartile range (IQR) was calculated to assess the median duration. Results: Among 86 pts, 43 received EV alone and 43 received EV/P, with a median age of 74. Most pts were male (69, 80%), with 59 reporting a history of smoking. Baseline neuropathy was present in 19 pts (22%). Prior cystectomy or nephroureterectomy was reported in 34 pts (39.5%). Overall, 59 pts (68%) discontinued EV for at least 8 weeks, 36 pts (84%) in EV alone, 23 pts (53%) in EV/P group. Most EV discontinuations were due to toxicity (52 pts, 60%). 12 pts (21%) discontinued due to complete response. The median duration of tx before EV discontinuation was 3.7 months (IQR 4.2), with 3.2 months (IQR 3.9) in the EV-alone group and 5.0 months (IQR 4.7) in the EV/P group. Following discontinuation, progression occurred in 34 of 56 (57%) pts, 23 in EV alone, and 11 in EV/P group. 39% pts remained disease-free despite discontinuing EV at the time of last follow-up. The median time to progression after treatment discontinuation was 5.92 months (IQR 5.06–10.85) overall, with 7.82 months (IQR 3.62–NA) in the EV/P group and 5.88 months (IQR 4.41–NA) in the EV-alone group. EV rechallenge was attempted in 23 of 56 (41%) pts discontinuing EV, and the median duration of EV rechallenge was 3.0 months (IQR 1.9).Upon EV re-challenge (N = 23), 5 pts had partial responses, 5 pts had stable disease, and 12 pts had progressive disease. No significant correlation was observed between the duration of EV tx before the tx discontinuation and response to EV upon re-challenge in either group (two-sided Mann-Whitney test p-value = 0.59. Conclusions: This study highlights that tx discontinuation due to toxicities is common in mUC pts receiving EV and EV/P. About 60% pts experienced disease progression after EV discontinuation with a median time to progression of 6 months. EV re-challenge was associated with responses in some pts and should be considered by those who may tolerate it.