Oncologic Outcomes of Patients with Immune Checkpoint Inhibitor Resistant Urothelial Carcinoma Treated with Enfortumab Vedotin and the Impact of Neutrophil-to-Lymphocyte Ratio and Dysgeusia on Overall Survival: A Retrospective Multicenter Cohort Study in Japan

Oncologic Outcomes of Patients with Immune Checkpoint Inhibitor Resistant Urothelial Carcinoma Treated with Enfortumab Vedotin and the Impact of Neutrophil-to-Lymphocyte Ratio and Dysgeusia on Overall Survival: A Retrospective Multicenter Cohort Study in Japan Keita Nakane Department of Urology, Gifu University Graduate School of Medicine, Gifu 5011194, Japan http://orcid.org/0000-0002-2589-1722 Kazuki Taniguchi Department of Urology, Gifu Prefectural General Medical Center, Gifu 5008717, Japan Minori Nezasa Department of Urology, Matsunami General Hospital, Gifu 5016062, Japan Torai Enomoto Department of Urology, Gifu University Graduate School of Medicine, Gifu 5011194, Japan Department of Urology, Matsunami General Hospital, Gifu 5016062, Japan Toyohiro Yamada Department of Urology, Ogaki Municipal Hospital, Ogaki 5038502, Japan Risa Tomioka-Inagawa Department of Urology, Japanese Red Cross Takayama Hospital, Takayama 5068550, Japan Kojiro Niwa Department of Urology, Daiyukai Daiichi Hospital, Ichinomiya 4918551, Japan Masayuki Tomioka Department of Urology, Gifu University Graduate School of Medicine, Gifu 5011194, Japan Department of Urology, Chuno Kosei Hospital, Seki 5013802, Japan Takashi Ishida Department of Urology, Gifu Municipal Hospital, Gifu 5008513, Japan Shingo Nagai Department of Urology, Toyota Memorial Hospital, Toyota 4718513, Japan Shigeaki Yokoi Department of Urology, Central Japan International Medical Center, Minokamo 5058510, Japan Tomoki Taniguchi Department of Urology, Gifu University Graduate School of Medicine, Gifu 5011194, Japan http://orcid.org/0000-0002-2612-2191 Makoto Kawase Department of Urology, Gifu University Graduate School of Medicine, Gifu 5011194, Japan http://orcid.org/0000-0001-7269-2462 Kota Kawase Department of Urology, Gifu University Graduate School of Medicine, Gifu 5011194, Japan Koji Iinuma Department of Urology, Gifu University Graduate School of Medicine, Gifu 5011194, Japan Yuki Tobisawa Department of Urology, Gifu University Graduate School of Medicine, Gifu 5011194, Japan Takuya Koie Department of Urology, Gifu University Graduate School of Medicine, Gifu 5011194, Japan http://orcid.org/0000-0002-2980-127X

Randomized phase III trial results have demonstrated enfortumab vedotin (EV), an antibody–drug conjugate (ADC) consisting of an anti-Nectin-4 human IgG1 monoclonal antibody and monomethyl auristatin E, is a useful treatment for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) that progressed after immune checkpoint inhibitor (ICI) therapies. This multicenter retrospective cohort study aimed to identify predictive factors for the efficacy of EV therapy and prolonged overall survival (OS) of patients in clinical practice. This study included patients with la/mUC who received ICI treatment. Patients who subsequently received EV treatment, those who received non-EV chemotherapy, and those who received no treatment were defined as EV, non-EV, and best supportive care (BSC) groups, respectively. The median OS was 20, 15, and 7 months in the EV, non-EV, and BSC groups, respectively (p < 0.001). Patients with la/mUC who had a complete or partial response after EV treatment had a significantly prolonged OS compared with those with stable or progressive disease. Univariate analysis showed age, neutrophil-to-lymphocyte ratio (NLR), dysgeusia, and rash as independent predictors of OS improvement. NLR and dysgeusia were independent predictors of OS after EV in multivariate analysis. Patients without these factors had a significantly prolonged OS compared to those with both factors. In real-world practice, EV therapy is an effective treatment for patients with la/mUC after ICI treatment.
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