Induction avelumab followed by chemoimmunotherapy and maintenance versus chemotherapy alone as first-line therapy in cis-ineligible metastatic urothelial carcinoma (INDUCOMAIN): a randomized phase II study

Rodriguez-Vida, Alejo; Valderrama, Begoña P.; Castellano, Daniel; Pinto, Álvaro; Mellado, Begoña; Puente, Javier; Climent, Miguel Ángel; Doménech, Montserrat; Vazquez, Federico; Perez-Gracia, Jose Luis; Bonfill, Teresa; Morales-Barrera, Rafael; González-Billalabeitia, Enrique; Garcia-del-Muro, Xavier; Maroto, Pablo; Navarro-Gorro, Nil; Juanpere, Nuria; Juan, Oscar; Bellmunt Molins, Joaquim, 1959-

Induction avelumab followed by chemoimmunotherapy and maintenance versus chemotherapy alone as first-line therapy in cis-ineligible metastatic urothelial carcinoma (INDUCOMAIN): a randomized phase II study

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dc.contributor.author Rodriguez-Vida, Alejo
dc.contributor.author Valderrama, Begoña P.
dc.contributor.author Castellano, Daniel
dc.contributor.author Pinto, Álvaro
dc.contributor.author Mellado, Begoña
dc.contributor.author Puente, Javier
dc.contributor.author Climent, Miguel Ángel
dc.contributor.author Doménech, Montserrat
dc.contributor.author Vazquez, Federico
dc.contributor.author Perez-Gracia, Jose Luis
dc.contributor.author Bonfill, Teresa
dc.contributor.author Morales-Barrera, Rafael
dc.contributor.author González-Billalabeitia, Enrique
dc.contributor.author Garcia-del-Muro, Xavier
dc.contributor.author Maroto, Pablo
dc.contributor.author Navarro-Gorro, Nil
dc.contributor.author Juanpere, Nuria
dc.contributor.author Juan, Oscar
dc.contributor.author Bellmunt Molins, Joaquim, 1959-
dc.date.accessioned 2025-11-11T16:00:56Z
dc.date.available 2025-11-11T16:00:56Z
dc.date.issued 2024
dc.date.updated 2025-11-11T16:00:56Z
dc.description.abstract Background: Platinum-based chemotherapy (ChT) has been the standard first-line treatment for metastatic urothelial carcinoma (mUC). The purpose of this study was to evaluate the use of induction avelumab followed by avelumab in combination with carboplatin-gemcitabine (carbo/gem) followed by avelumab maintenance. We tested the hypothesis that induction immunotherapy (IO) could enhance the response to ChT and prevent its detrimental effect on immune cells. Materials and methods: INDUCOMAIN is a multicenter, randomized, investigator-initiated, open-label phase II study evaluating the safety and efficacy of induction avelumab before carboplatin-gemcitabine-avelumab, followed by avelumab maintenance (arm A), compared to carbo/gem (arm B). Eligibility criteria included patients with mUC, no prior systemic therapy, and ineligibility for cisplatin by Galsky criteria. Patients were stratified by the presence/absence of visceral metastasis and Eastern Cooperative Oncology Group performance status 0-1 versus 2. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results: Eighty-five patients were included and randomized to arm A (n = 42) and arm B (n = 43), respectively. ORR was similar between treatment arms: 59.5% in arm A and 53.5% in arm B (P = 0.57). Fourteen patients (33%) in arm A early progressed/died before or at first response assessment, compared to three patients (7%) in arm B. Median OS was 11.1 months in arm A and 13.2 months in arm B [hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.57-1.46, P = 0.69]. Median PFS was 6.9 months in arm A versus 7.4 months in arm B (HR 0.99, 95% CI 0.61-1.60, P = 0.95). Treatment-related adverse events of grade 3-4 occurred in 70.7% of patients in arm A and in 72.1% in arm B. No predictive role of programmed death-ligand 1 expression was found. Conclusions: The hypothesis that induction avelumab could enhance the efficacy of subsequent ChT was not proven. Administering IO alone as induction before ChT is not an adequate strategy.
dc.format.mimetype application/pdf
dc.identifier.citation Rodriguez-Vida A, Valderrama BP, Castellano D, Pinto A, Mellado B, Puente J, Climent MA, Domenech M, Vazquez F, Perez-Gracia JL, Bonfill T, Morales-Barrera R, Gonzalez-Billalabeitia E, Garcia-Del-Muro X, Maroto P, Navarro-Gorro N, Juanpere N, Juan O, Bellmunt J. Induction avelumab followed by chemoimmunotherapy and maintenance versus chemotherapy alone as first-line therapy in cis-ineligible metastatic urothelial carcinoma (INDUCOMAIN): a randomized phase II study. ESMO Open. 2024 Sep;9(9):103690. DOI: 10.1016/j.esmoop.2024.103690
dc.identifier.doi http://dx.doi.org/10.1016/j.esmoop.2024.103690
dc.identifier.issn 2059-7029
dc.identifier.uri http://hdl.handle.net/10230/71862
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof ESMO Open. 2024;9(9):103690
dc.rights © 2024 The Author(s). Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.keyword Metastatic urothelial carcinoma
dc.subject.keyword Avelumab
dc.subject.keyword Cisplatin-ineligible
dc.subject.keyword Induction immunotherapy
dc.subject.keyword First-line therapy
dc.title Induction avelumab followed by chemoimmunotherapy and maintenance versus chemotherapy alone as first-line therapy in cis-ineligible metastatic urothelial carcinoma (INDUCOMAIN): a randomized phase II study
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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