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. 2024 Nov;19(6):905-915.
doi: 10.1007/s11523-024-01099-0. Epub 2024 Oct 1.

Enfortumab Vedotin Following Platinum Chemotherapy and Avelumab Maintenance in Patients with Metastatic Urothelial Carcinoma: A Retrospective Data from the ARON-2EV Study

Ondřej Fiala #  1   2 , Francesco Massari #  3   4 , Umberto Basso  5 , Patrizia Giannatempo  6 , Enrique Grande  7 , Sebastiano Buti  8   9 , Zin W Myint  10 , Ugo De Giorgi  11 , Renate Pichler  12 , Francesco Grillone  13 , Yüksel Ürün  14 , Fabio Calabrò  15 , Maria T Bourlon  16   17 , Luca Galli  18 , Ravindran Kanesvaran  19 , Giandomenico Roviello  20 , Jakub Kucharz  21 , Mimma Rizzo  22 , Se Hoon Park  23 , Linda Cerbone  24 , Emmanuel Seront  25 , Carlo Messina  26 , Javier Molina-Cerrillo  27 , Daniele Santini  28 , Akihiro Yano  29 , Lorena Incorvaia  30 , Martina Catalano  19 , Alvaro Pinto  31 , Luigi Formisano  32 , Andrey Soares  33   34 , Gaetano Facchini  35 , Giuseppe Fornarini  36 , Alexandr Poprach  37   38 , Sara Elena Rebuzzi  39   40 , Cecilia Nasso  41 , Gian Paolo Spinelli  42 , Martin Angel  43 , Marco Stellato  6 , Deniz Tural  44 , Gaetano Aurilio  45 , Ilana Epstein  46 , Francesco Carrozza  47 , Fernando Sabino Marques Monteiro  48   49 , Giovanni Benedetti  50 , Tomáš Büchler  51 , Cinzia Ortega  52 , Roubini Zakopoulou  53 , Nicola Battelli  54 , Camillo Porta  55 , Joaquin Bellmunt  56   46 , Shilpa Gupta #  57 , Matteo Santoni #  54
Affiliations

Enfortumab Vedotin Following Platinum Chemotherapy and Avelumab Maintenance in Patients with Metastatic Urothelial Carcinoma: A Retrospective Data from the ARON-2EV Study

Ondřej Fiala et al. Target Oncol. 2024 Nov.

Abstract

Background: Enfortumab vedotin (EV) has been approved for the treatment of patients with locally advanced/metastatic urothelial carcinoma (la/mUC) who previously received platinum-based chemotherapy followed by immune checkpoint inhibitors. However, the pivotal clinical trials did not include patients previously treated with avelumab maintenance therapy.

Objective: The aim of the present retrospective analysis was to assess the effectiveness of EV following avelumab in patients with mUC enrolled in the ARON-2EV study.

Patients and methods: The study included 182 patients with mUC treated with EV following avelumab maintenance. The primary objective was to assess clinical outcomes, including progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and duration of response (DoR). Statistical analysis involved Fisher exact test, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models.

Results: Median OS and PFS were 12.7 (95% CI 10.2-14.1) and 7.9 (95% CI 6.4-9.9) months, respectively. Complete response (CR) was achieved in 5% and partial response (PR) in 34% of patients, with an ORR of 39%. The DoR in patients who achieved CR/PR was 10.9 months (95% CI 8.1-11.4). The incidence of grade ≥ 3 peripheral neuropathy and skin rash was 9%, followed by 8% of grade ≥ 3 diarrhea and 4% of grade ≥ 3 hyperglycemia.

Conclusions: The results of our large international retrospective study confirm the effectiveness of EV and endorse its use in the population of patients with mUC treated with EV following the frontline platinum-based chemotherapy and subsequent maintenance treatment with avelumab.

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Conflict of interest statement

Declarations Funding No external funding was used in the preparation of this manuscript. Conflicts of Interest Ondřej Fiala received honoraria from Roche, Janssen, GSK, and Pfizer for consultations and lectures unrelated to this project. Francesco Massari has received research support and/or honoraria from Advanced Accelerator Applications, Astellas, Astra Zeneca, Bayer, BMS, Janssen, Ipsen, MSD, and Pfizer outside the submitted work. Umberto Basso received honoraria for Bristol-Myers Squibb, Novartis, and Astra Zeneca; research funding from Ipsen; and travel grants from Bristol-Myers Squibb, Janssen Oncology, Astellas Pharma, MSD Oncology, Merck/Pfizer, and Bayer, all unrelated to this project. Sebastiano Buti received honoraria as speaker at scientific events and advisory role by BMS, Pfizer, MSD, Ipsen, Roche, Eli Lilly, AstraZeneca, Pierre-Fabre, Novartis, Merck, Gentili, and Astellas, all unrelated to the present paper. Yüksel Ürün has served on advisory board for Abdi-İbrahim, Astellas, AstraZeneca, Bristol Myers-Squibb, Deva, Eczacıbaşı, Gen ilaç, Gilead, GSK, Janssen, Merck, MSD, Novartis, Pfizer, and Roche and received travel grants, honoraria, or consultation fees from Abdi-İbrahim, Astellas, Bristol Myers-Squibb, Deva, Eczacıbaşı, Gen İlaç, Gilead, GSK, Janssen, Merck, Novartis, Pfizer, and Roche, all unrelated to the present paper. Maria T. Bourlon is a consultant of Bristol Myers Squibb, Merck, MSD, Gilead, Astellas, and Asofarma and a speaker for Janssen Pharmaceuticasl, MSD, Merck, and Astellas, all unrelated to the present paper. Mimma Rizzo has received honoraria as a speaker/consultant by MSD, Merck Serono, Astrazeneca, Bristol Myers Squibb, Eisai, and Gilead, all unrelated to the present paper. Linda Cerbone has received honoraria for advisory boards, speaker engagements, and scientific consultancy for educational purposes from AstraZeneca, EISAI, MSD, Ipsen, BMS, and A.A.A.; and is a past MSD employee in Medical Affairs. Javier Molina-Cerrillo reports research funding from Roche, Ipsen, Pfizer, and Janssen; travel support from Pfizer, Janssen, Ipsen, and BMS; and a consulting or advisory role with Ipsen, Roche, BMS, Pfizer, Sanofi, Janssen, Astellas, Eisai, Adium, and MSD, all unrelated to the present paper. Álvaro Pinto is a member of advisory boards of Pfizer, Novartis, Ipsen, BMS, Janssen, Astellas, Sanofi, Bayer, Clovis, Roche, MSD, Pierre Fabre, and Merck; has received research support from Pfizer and BMS; clinical trial payments from Pfizer, Bayer, Janssen, MSD, Clovis, Pharmacyclics, BMS, Sanofi, Astra Zeneca, Roche, Eisai, and Aveo; and travel arrangements from Janssen, Roche, Pfizer, BMS, and Ipsen, all unrelated to the present paper. Andrey Soares reports honoraria from Janssen, Pfizer, Bayer, AstraZeneca, Astellas Pharma, Merck Serono, Sanofi, Ipsen, and Adium; consulting or advisory role from Astellas Pharma, Janssen, Roche, Bayer, AstraZeneca, MSD, Bristol-Myers Squibb, Adium, Ipsen, Pfizer, and Novartis; research funding from Bristol-Myers Squibb (Inst), Astellas (Inst), and AstraZeneca (Inst); travel, accommodations, and expenses from Bayer, Janssen, Ipsen, Adium, MSD, and Merck Serono; and ownership in BIO, Brazilian Information Oncology; all unrelated to this study. Alexandr Poprach has received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from BMS, Ipsen, Roche, Astellas, Merck, Eisai, MSD, Novartis, and Pfizer, unrelated to this project. Gian Paolo Spinelli has received payment or honoraria for advidory boards from Novartis, Roche, and Bayer, unrelated to this project. Martin Angel received honoraria from Roche, Johnson & Johnson, Raffo, and Pfizer for consultations and lectures unrelated to this project. Fernando Sabino M. Monteiro reports research support provided by Merck Sharp Dome; honoraria from Janssen, Ipsen, Bristol Myers Squibb, and Merck Sharp Dome; and ownership in BIO, Brazilian Information Oncology, all unrelated to this study. Camillo Porta acted as a remunerated consultant and/or speaker for Angelini Pharma, AstraZeneca, BMC, Eisai, Exilixis, Genenta, Ipsen, Merck Serono, and MSD; as a protocol steering committee member for Eisai and MSD; and as an Independent Review Board member for Genenta. Shilpa Gupta is a consultant for Bristol Myers Squibb, Merck, Pfizer, Gilead, Bayer, and Seattle Genetics; is a speaker for Bristol Myers Squibb; and has institutional research funding from Seatte Genetics, Pfizer, Merck, Bristol Myers Squibb, Roche, Novartis, and Tyra Biosciences. Matteo Santoni has received research support and honoraria from Janssen, Bristol Myers Squibb, Ipsen, MSD, Astellas, and Bayer, all unrelated to the present paper. Patrizia Giannatempo, Enrique Grande, Zin W. Myint, Ugo De Giorgi, Renate Pichler, Francesco Grillone, Fabio Calabrò, Luca Galli, Ravindran Kanesvaran, Giandomenico Roviello, Jakub Kucharz, Se Hoon Park, Emmanuel Seront, Carlo Messina, Daniele Santini, Akihiro Yano, Lorena Incorvaia, Martina Catalano, Luigi Formisano, Gaetano Facchini, Giuseppe Fornarini, Sara Elena Rebuzzi, Cecilia Nasso, Marco Stellato, Deniz Tural, Gaetano Aurilio, Ilana Epstein, Francesco Carrozza, Giovanni Benedetti, Tomáš Büchler, Cinzia Ortega, Roubini Zakopoulou, Nicola Battelli, and Joaquin Bellmunt declare that they have no conflicts of interest that might be relevant to the contents of this manuscript. Tomáš Büchler and Camillo Porta are Editorial Board members of Targeted Oncology. Tomáš Büchler and Camillo Porta were not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Ethics Approval The study protocol was approved on 28 September 2023, by the Ethical Committee of the coordinating center (Marche Region – Italy – no. 2022 39/7875, Study Protocol “ARON 2 Study” NCT05290038) and by the Institutional Review Boards of participating centers. Consent to Participate Informed consent with subsequent analysis of the follow-up data was obtained from all participants. Consent for Publication Not applicable. Availability of Data and Material The datasets generated and/or analyzed during the current study are not publicly available due to patient data security but are available from the corresponding author on reasonable request. Code Availability Not applicable. Author Contributions Study concept and design: all authors; acquisition of data: all authors; analysis and interpretation of data: all authors; drafting of the manuscript: Fiala, Massari, Gupta, and Santoni; critical revision of the manuscript for important intellectual content: all authors; statistical analysis: Santoni; obtaining funding: none; administrative, technical, or material support: none; and supervision: Gupta and Santoni.

Figures

Fig. 1
Fig. 1
Overall survival and progression-free survival for patients treated with enfortumab vedotin for metastatic urothelial carcinoma following avelumab maintenance therapy
Fig. 2
Fig. 2
Overall survival for patients treated with enfortumab vedotin for metastatic urothelial carcinoma following avelumab maintenance therapy stratified by Eastern Cooperative Oncology Group Performance Status (ECOG-PS)
Fig. 3
Fig. 3
Progression-free survival (PFS) for enfortumab vedotin according to the median PFS of previous avelumab maintenance therapy
Fig. 4
Fig. 4
Objective response to enfortumab vedotin (EV) according to the objective response to avelumab maintenance therapy prior to EV. EV enfortumab vedotin, CR complete response, PR partial response, SD stable disease, PD progressive disease
See this image and copyright information in PMC

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