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. 2025 Jul 18;15(1):26127.
doi: 10.1038/s41598-025-09806-1.

Efficacy of modified enfortumab vedotin ineligible criteria (mEVITA) in advanced urothelial carcinoma

Takafumi Fukushima  1 , Kazuyuki Numakura  2 , Masanao Shinohara  3 , Yohei Kawashima  3 , Yuya Sekine  2 , Kanami Mori  2 , Mizuki Kobayashi  2 , Himawari Asanuma  1 , Takaki Ichiyama  1 , Hisashi Sakurai  1 , Kai Ozaki  1 , Naoki Fujita  1 , Teppei Okamoto  1 , Hayato Yamamoto  1 , Takahiro Yoneyama  4 , Satoshi Sato  3 , Tomonori Habuchi  2 , Chikara Ohyama  5 , Shingo Hatakeyama  6
Affiliations

Efficacy of modified enfortumab vedotin ineligible criteria (mEVITA) in advanced urothelial carcinoma

Takafumi Fukushima et al. Sci Rep. .

Abstract

Enfortumab Vedotin Ineligible criTeriA (EVITA) were proposed for the selection of patients to receive enfortumab vedotin (EV) and pembrolizumab treatment. However, the usefulness of these criteria has not been fully verified. We retrospectively analyzed data from 301 patients with unresectable or metastatic urothelial carcinoma who underwent first-line chemotherapy and 135 patients with EV monotherapy in real-world practice. We evaluated the numbers of patients fulfilling the modified EVITA (mEVITA; excluding ocular abnormalities) and the relationship of the mEVITA to the safety and efficacy in patients with EV monotherapy. Of the 301 patients who received first-line chemotherapy, 4.3% (n = 13) met the mEVITA criteria. The primary factor contributing to mEVITA ≥ 2 was renal dysfunction. Of the 135 patients who underwent subsequent EV therapy, the number of the mEVITA had no influence on the frequency of all-grade and grade ≥ 3 adverse events. However, the mEVITA ≥ 2 was significantly associated with temporary EV interruption. Oncological outcomes were not associated with the number of the mEVITA. In conclusion, 4.3% and 14.8% of patients met the mEVITA criteria at the time of first-line and subsequent EV therapy, respectively. Having mEVITA ≥ 2 may be associated with temporary interruption of EV therapy.

Keywords: EVITA; Efficacy; Enfortumab Vedotin; Safety; Urothelial carcinoma.

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Conflict of interest statement

Declarations. Competing interests: Shingo Hatakeyama received honoraria from Janssen Pharmaceutical K.K., Astellas Pharma Inc., AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Bayer AG, Pfizer Inc., Bristol-Myers Squibb, Merck Biopharma Co., Ltd., Kaneka Corporation, and Nipro Corporation. The other authors have no conflicts of interest to declare. Consent for publication: All authors approved for the publication. Disclosure of conflicts of interest: Shingo Hatakeyama received honoraria from Janssen Pharmaceutical K.K., Astellas Pharma Inc., AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Bayer AG, Pfizer Inc., Bristol-Myers Squibb, Merck Biopharma Co., Ltd., Kaneka Corporation, and Nipro Corporation. The other authors have no conflicts of interest to declare. Consent to participate: Written consent was not obtained in exchange for the public disclosure of study information (opt-out approach) by an Institutional Review Board by the ethics committee of the Hirosaki University School of Medicine (approval nos. 2019-099-2 and 2021-158-2, opt-out approach).

Figures

Fig. 1
Fig. 1
Study design and analysis. This study included 301 patients with unresectable or metastatic urothelial carcinoma. Of the 301 patients, 135 underwent subsequent EV monotherapy. EV = enfortumab vedotin; mEVITA = modified Enfortumab Vedotin Ineligible criTeriA. The percentages refer to subgroup totals.
Fig. 2
Fig. 2
Proportion of the mEVITA population. (A) Percentage of patients who met the mEVITA at the time of first-line chemotherapy and subsequent EV monotherapy. (B) Factors of mEVITA and their prevalence. The percentages refer to subgroup totals. mEVITA = modified Enfortumab Vedotin Ineligible criTeriA. *, The number of patients with mEVITA ≥ 2 in 1st-line chemotherapy vs. subsequent EV.
Fig. 3
Fig. 3
Association of the mEVITA with safety and efficacy (additional secondary analysis). (A) The association of the mEVITA and adverse events (AEs). (B) The association of eGFR and AEs. (C) The association of the mEVITA and EV dose reduction or temporary EV interruption. (D) The association of the mEVITA ≥ 2 and temporary EV interruption. (E) The association of the mEVITA and objective response rate (ORR). (F) The association of the mEVITA and overall survival after EV monotherapy. The percentages refer to subgroup totals. eGFR = estimated glomerular filtration rate; EV = enfortumab vedotin; mEVITA = modified Enfortumab Vedotin Ineligible criTeriA.
Fig. 4
Fig. 4
Factors associated with adverse event (AE)–related EV discontinuation. (A) The association of the mEVITA and AE-related EV discontinuation. (B) The association of the mEVITA ≥ 2 and AE-related EV discontinuation. (C) The association of grade ≥ 3 AE and AE-related EV discontinuation. (D) EV discontinuation by type of AE. (E) Logistic regression analysis for AE-related EV discontinuation. The percentages refer to subgroup totals. EV = enfortumab vedotin; mEVITA = modified Enfortumab Vedotin Ineligible criTeriA; G-I tract = gastrointestinal tract.
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