Abstract Objective Combination therapy with enfortumab vedotin (EV) and pembrolizumab has shown superior overall survival (OS) compared to platinum-based chemotherapy in advanced urothelial carcinoma (UC). Given the expanding landscape of first-line treatments, understanding site-specific effectiveness is vital for developing individualized strategies. Methods We conducted a retrospective analysis of 225 patients with advanced UC treated between April 2009 and August 2024. Systemic therapy efficacy was assessed in relation to metastatic site, focusing on site-specific responses. Patients were classified into three treatment periods (chemotherapy period April 2009–June 2017; P1, pembrolizumab period July 2017–December 2020; P2, and avelumab and EV period January 2021–August 2024; P3). Within each period, patients were stratified by metastatic pattern—lymph node-only, liver, or other—and OS was analyzed accordingly. Results The objective response rates for chemotherapy, pembrolizumab, avelumab, and EV were 41%, 23%, 20%, and 46%, respectively. Lymph node and pulmonary metastases exhibited favorable responses across all treatment modalities, whereas bone metastases consistently responded poorly. Notably, EV exhibited substantial activity against liver metastases. Median OS improved over successive treatment periods (P1: 14 months; P2: 16 months; P3: 26 months). However, patients with liver metastases experienced no meaningful OS improvement (P1: 9.5 months; P2: 9.2 months; P3: 8 months), with 54% of these patients not receiving EV. Conclusions Sequential therapies may offer a survival benefit in selected patients. EV plus pembrolizumab may be particularly beneficial in patients with rapidly progressive disease such as those with liver metastases, warranting further investigation in real-world settings.
Yamamoto et al. (Wed,) studied this question.