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Comparative Study
. 2024 Feb 3;31(2):862-871.
doi: 10.3390/curroncol31020064.

Prognostic Impact of Histologic Subtype and Divergent Differentiation in Patients with Metastatic Urothelial Carcinoma Treated with Enfortumab Vedotin: A Multicenter Retrospective Study

Akinori Minato  1 , Nobuki Furubayashi  2 , Yujiro Nagata  1 , Toshihisa Tomoda  3 , Hiroyuki Masaoka  4 , Yoohyun Song  4 , Yoshifumi Hori  5 , Keijiro Kiyoshima  6 , Takahito Negishi  2 , Kentaro Kuroiwa  5 , Narihito Seki  4 , Ikko Tomisaki  1 , Kenichi Harada  1 , Motonobu Nakamura  2 , Naohiro Fujimoto  1
Affiliations
Comparative Study

Prognostic Impact of Histologic Subtype and Divergent Differentiation in Patients with Metastatic Urothelial Carcinoma Treated with Enfortumab Vedotin: A Multicenter Retrospective Study

Akinori Minato et al. Curr Oncol. .

Abstract

Subtype of urothelial carcinoma (SUC), defined here as urothelial carcinoma with any histologic subtype or divergent differentiation, is a clinically aggressive disease. However, the efficacy of enfortumab vedotin (EV) against SUC remains unclear. Hence, this study aimed to assess the oncological outcomes of patients with SUC treated with EV for metastatic disease. We retrospectively evaluated consecutive patients with advanced lower and upper urinary tract cancer who received EV after platinum-based chemotherapy and immune checkpoint blockade therapy at six institutions. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared between patients with pure urothelial carcinoma (PUC) and those with SUC. We identified 44 and 18 patients with PUC and SUC, respectively. Squamous differentiation was the most common subtype element, followed by glandular differentiation and sarcomatoid subtype. Although patients with SUC had a comparable ORR to those with PUC, the duration of response for SUC was short. Patients with SUC had poorer PFS than those with PUC; however, no significant difference was observed in OS. Multivariate analysis revealed that SUC was significantly associated with shorter PFS. Although the response of metastatic SUC to EV was similar to that of PUC, SUC showed faster progression than PUC.

Keywords: antibody–drug conjugate; divergent differentiation; enfortumab vedotin; histologic subtype; metastatic urothelial carcinoma; prognosis; survival; variant histology.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Kaplan–Meier curves for the duration of response (complete or partial responders) to enfortumab vedotin in patients with PUC and SUC. Abbreviations: PUC, pure urothelial carcinoma; SUC, subtype of urothelial carcinoma.
Figure 2
Figure 2
Kaplan–Meier curves for (a) progression-free survival and (b) overall survival after enfortumab vedotin initiation in patients with PUC and SUC. Abbreviations: PUC, pure urothelial carcinoma; SUC, subtype of urothelial carcinoma.
See this image and copyright information in PMC

References

    1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Bajorin D.F., Witjes J.A., Gschwend J.E., Schenker M., Valderrama B.P., Tomita Y., Bamias A., Lebret T., Shariat S.F., Park S.H., et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N. Engl. J. Med. 2021;384:2102–2114. doi: 10.1056/NEJMoa2034442. - DOI - PMC - PubMed
    1. Powles T., Park S.H., Voog E., Caserta C., Valderrama B.P., Gurney H., Kalofonos H., Radulović S., Demey W., Ullén A., et al. Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma. N. Engl. J. Med. 2020;383:1218–1230. doi: 10.1056/NEJMoa2002788. - DOI - PubMed
    1. Bellmunt J., de Wit R., Vaughn D.J., Fradet Y., Lee J.L., Fong L., Vogelzang N.J., Climent M.A., Petrylak D.P., Choueiri T.K., et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N. Engl. J. Med. 2017;376:1015–1026. doi: 10.1056/NEJMoa1613683. - DOI - PMC - PubMed
    1. Powles T., Rosenberg J.E., Sonpavde G.P., Loriot Y., Durán I., Lee J.L., Matsubara N., Vulsteke C., Castellano D., Wu C., et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. N. Engl. J. Med. 2021;384:1125–1135. doi: 10.1056/NEJMoa2035807. - DOI - PMC - PubMed

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