Treatment patterns and outcomes with second-line therapies in patients with advanced urothelial carcinoma previously treated with first-line enfortumab vedotin with pembrolizumab

Enfortumab vedotin with pembrolizumab (EV + pembro) has transformed first-line treatment of advanced urothelial carcinoma (aUC). No prospective data are available evaluating outcomes of different therapies following progression on EV + pembro. Patients who received first-line EV + pembro and had second-line therapy data available were eligible and included. Second-line treatment types were categorized as cisplatin-based therapy, carboplatin-based therapy, EV rechallenge, or other. Outcomes assessed included real-world overall survival (rwOS) and real-world time to next therapy (rwTTNT). Among 15,236 pts with aUC, 757 received first-line EV + pembro, and 118 who went on to second-line therapy and had survival outcomes were included. Second-line treatments were carboplatin-based (35%), cisplatin-based (13%), other regimens (38%), and EV rechallenge (13%). The “Other” category included erdafitinib, trastuzumab deruxtecan, and sacituzumab govitecan. Median rwTTNT ranged from 3–4.7 months for platinum regimens to 8.5 months with EV rechallenge. Median rwOS ranged 7.1–8.5 months for platinum-base therapy or EV rechallenge and 14 months for other regimens. This is the largest real-world study to date evaluating real-world treatment patterns and outcomes with various second-line therapies after progression on first-line EV + pembro in aUC. Median rwOS and rwTTNT were modest across all treatment groups. These findings underscore the limited efficacy of current second-line options in the post EV + pembro setting.