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.