Real-world incidence of interstitial lung disease with enfortumab vedotin plus pembrolizumab or enfortumab vedotin monotherapy in metastatic urothelial carcinoma: a multicenter retrospective study in Japan

Background Enfortumab vedotin (EV) plus pembrolizumab is a standard first-line therapy for locally advanced or metastatic urothelial carcinoma. Interstitial lung disease (ILD) is a potentially serious adverse event (AE) associated with these therapies. We compared the incidence of ILD between EV monotherapy and enfortumab vedotin plus pembrolizumab in Japanese clinical practice. Methods This multicenter retrospective study included patients with locally advanced or metastatic urothelial carcinoma treated with EV or EV plus pembrolizumab at five Japanese institutions. AEs, particularly ILD, were compared between the two groups. Factors associated with ILD development were evaluated using Firth penalized logistic regression. Results Among 141 patients, 81 received EV and 60 received EV plus pembrolizumab. Grade ≥ 3 AEs were more frequent with the combination (27% vs. 10%, P = .0106). ILD occurred significantly more frequently in the combination (12% vs. 2%, P = .0272). Grade ≥3 ILD occurred in 8% versus 2% (P = .11). In Firth penalized logistic regression analysis adjusted for age and Eastern Cooperative Oncology Group performance status, the combination was associated with ILD (adjusted odds ratio, 5.47; 95% confidence interval, 1.32–32.3; P = .0134). Conclusions In this retrospective Japanese cohort, ILD was observed more frequently in patients receiving enfortumab vedotin plus pembrolizumab than in those receiving enfortumab vedotin monotherapy. Careful monitoring and early recognition of ILD are warranted during combination therapy.