Enfortumab vedotin following platinum-based chemotherapy and immune checkpoint inhibitors for advanced urothelial carcinoma: response, survival and safety analysis from a multicentre real-world Japanese cohort

Abstract

Objective Real-world evidence regarding enfortumab vedotin for unresectable or metastatic urothelial carcinoma is scarce, particularly in Japan. We investigated real-world data focusing on patient background, previous treatments, response, survival and adverse events in patients receiving enfortumab vedotin. Methods A multicentre database was used to register 556 patients diagnosed with metastatic urothelial carcinoma from 2008 to 2023; 34 patients (6.1%) treated with enfortumab vedotin were included. Best radiographic objective responses were evaluated using the Response Evaluation Criteria in Solid Tumors (v1.1) during treatments. Overall survival and progression-free survival were estimated (Kaplan–Meier method). Toxicities were reported according to the Common Terminology Criteria for Adverse Events, version 5.0. The relative dose intensity, which could impact oncological outcomes, was calculated. Results The median number of enfortumab vedotin therapy cycles was 5. The best objective response to enfortumab vedotin was partial response, stable disease and progressive disease in 19 (56%), 5 (15%) and 10 (29%) patients, respectively. The median overall survival and progression-free survival after the first enfortumab vedotin dose were 16 and 9 months, respectively. No significant relationship was observed between survival outcomes after enfortumab vedotin initiation and the enfortumab vedotin relative dose intensity. The median overall survival from first-line platinum-based chemotherapy initiation was 42 months. Twenty-six (76%) patients experienced any grade of enfortumab vedotin-related toxicities; eight (24%) experienced Grades 3–4 toxicities, the most common being skin toxicity (any grade, 47%; Grades 3–4, 12%). Conclusions Here, we report real-world evidence for enfortumab vedotin therapy in Japan. Tumour responses and safety profiles were comparable with those of clinical trials on this novel treatment.

Real-World Insights into Efficacy and Safety of Enfortumab Vedotin in Japanese Patients with Metastatic Urothelial Carcinoma: Findings, Considerations, and Future Directions

“…Notably, the response rate for pure UC reached 58%, contrasting with 42% in patients with subtype histology [9]. In these two Japanese reports, subtype information is not available [10,11]. In our study, the response rate among patients with histological subtypes was 25% (2/8), with a response rate of 75% in those with pure UC, mirroring the UNITE study [9].…”

“…In two other multicenter retrospective studies from Japan, Taguchi et al reported that the ORR was 46%, and the median PFS and OS from the start of EV were 5 and 11 months, respectively, in 39 patients from nine institutions. Additionally, Miyake et al reported that the ORR was 56% (CR, 0%; PR, 0%), and the median PFS and OS from the start of EV were 9 and 16 months, respectively, in 34 patients from 19 institutions [10,11]. These retrospective studies concluded that the efficacy of EV therapy in real-world settings was comparable to that reported in clinical trials.…”

“…The EV-301 trial also reported that 19% of participants experienced serious AEs, 13.5% had AEs that led to treatment discontinuation, and 2.4% experienced AEs that led to death [8]. Miyake et al's multi-institutional study reported that 76% of patients experienced any-grade AEs, with 24% of serious AEs and 15% of AEs leading to the discontinuation of EV therapy [11]. In our study, with 35% of serious AEs and no AEs leading to treatment discontinuation, we observed a higher overall incidence of AEs compared to Miyake et al's report, primarily due to AEs resulting from prior subsequent therapies.…”

C-Reactive Protein Is a Potential Prognostic Marker in Patient with Advanced or Metastatic Urothelial Carcinoma Treated with Enfortumab Vedotin: A Multi-Center Retrospective Study

“…However, the biomarker analysis of EV treatment was very limited [24][25][26]. In the past, potential prognostic variables were identified that included a variety of inflammation and nutritional markers such as CRP, NLR, and the platelet-lymphocyte ratio [16][17][18][19]. In particular, concerning the value of the prognostic biomarker of CRP in the analysis, Klumper et al highlighted that the CRP response predicts immunotherapy response and outcomes in mUC independently in the 154 patients with mUC in the multi-center observational study by [16].…”

“…Additionally, when the GNRI is high, this may predict a good prognosis in those patients with la/mUC treated with ICIs. Moreover, several studies showed that the serum C-Reactive Protein (CRP), a marker of inflammation, was a prognostic marker in the systemic therapy including EV for la/mUC [13][14][15][16][17][18][19]. However, there was no evidence as to whether the GNRI or CRP was a better prognostic marker of EV therapy.…”