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Publications

Journal Article Epublish

PubMed: 42927021 DOI: 10.1016/j.esmorw.2026.100804

Skin toxicity and effectiveness of first-line enfortumab vedotin plus pembrolizumab for urothelial carcinoma: a prospective multicenter real-world study in Japan.

ESMO Real World Data Digit Oncol 14:100804

Authors: K Tamura, T Tsujino, R Taoka, K Kobayashi, M Miyake, K Ogawa, Y Sasaki, S Tatarano, S Katayama, M Kato, H Fukuhara, Y Abe, Y Oda, R Minato, R Shigehisa, R Maenosono, M Sugimoto, K Shiraishi, K Fujimoto, K Wada, J Furukawa, H Enokida, M Araki, J Uchida, K Inoue, T Inamoto

Affiliations

  • Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
  • Department of Urology, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan.
  • Department of Urology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
  • Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
  • Department of Urology, Nara Medical University, Kashihara, Japan.
  • Department of Urology, Shimane University Faculty of Medicine, Izumo, Japan.
  • Department of Urology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
  • Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
  • Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
  • Department of Urology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
  • Department of Urology, Kochi Medical School, Kochi University, Kochi, Japan.

Abstract

BACKGROUND

Skin toxicity is a common adverse event associated with enfortumab vedotin plus pembrolizumab (EVP) but its association with treatment outcomes remains unclear. We aimed to evaluate this association in patients with locally advanced or metastatic urothelial carcinoma (la/mUC).

PATIENTS AND METHODS

This prospective multicenter observational study conducted in Japan enrolled patients receiving first-line EVP. Skin toxicity incidence, onset, and management were evaluated. Objective response rates (ORRs) were compared according to the development of skin toxicity within 42 days. Progression-free survival (PFS) was assessed using a prespecified 42-day landmark analysis and a time-dependent Cox model to account for immortal time bias.

RESULTS

Among 163 assessable patients, 94 (57.7%) developed skin toxicity at a median of 13 days, of whom 81 (86.2%) recovered. Patients with skin toxicity within 42 days had a higher ORR than those without (70.1% versus 44.2%, P < 0.001). In the landmark cohort (n = 144), skin toxicity was associated with longer PFS [hazard ratio (HR) 0.43, 95% confidence interval (CI) 0.22-0.84, log-rank P = 0.011]. In multivariable time-dependent Cox analysis, skin toxicity remained independently associated with longer PFS (HR 0.44, 95% CI 0.23-0.83, P = 0.011).

CONCLUSION

Skin toxicity associated with first-line EVP was frequent, occurred early, and was generally manageable. Its development was associated with a higher ORR and its association with longer PFS persisted after accounting for immortal time bias. Skin toxicity may serve as a potential on-treatment prognostic indicator of favorable outcomes, although further validation is warranted.

MeSH

Skin, Bias, Therapeutics