Second-line platinum-based chemotherapy (PBT) in patients with metastatic urothelial carcinoma (mUC) treated with first-line pembrolizumab plus enfortumab vedotin (P/EV): A single-center, retrospective study.

785 Background: Although the efficacy of PBT as first-line therapy for mUC has been known for more than 30 years, the recent integration of P/EV as a preferred first-line option prevented the use of evidence-based regimen. Since the available second-line regimens depend on what was given as first-line, we evaluate the efficacy and tolerability of second-line PBT in mUC patients treated with first-line P/EV. Methods: We retrospectively reviewed the medical records of 37 patients with mUC who were treated with first-line P/EV, mostly in clinical trials, between Jan 2022 and Jan 2024 at Samsung Medical Center (Seoul, Korea). Patients with mUC whose disease progressed during or after first-line treatment with P/EV received PBT involving gemcitabine plus either cisplatin or carboplatin (determined on the basis of cisplatin-eligibility). Primary endpoints included safety and response rates. Results: Among a total of 37 first-line P/EV patients, 10 received second-line PBT: gemcitabine plus cisplatin (n = 8) and plus carboplatin (n = 2). The median age was 68 years (range, 48 to 82 years) and the median interval from the last dose of P/EV was 50 days (range, 15 to 89 days). A total of 33 PBT cycles were given (median, 2; range 1 to 6). One patient achieved a complete response and 3 had a stable disease. Although peripheral neuropathy and gastrointestinal toxicities were the most frequently encountered adverse events, safety profile was generally manageable. Median progression-free and overall survivals were 3.4 months (95% CI, 2.3 to 4.5) and 8.0 months (95% CI, 6.1 to 19.9), respectively. Conclusions: Second-line PBT for mUC patients treated with first-line P/EV does not appear highly active but the observation of responders merits further studies in those with medically-fit, platinum-eligible patients.