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

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 aveluma...

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Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p17699
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/17699
Access Level:acceso abierto
Palabra clave:metastatic urothelial carcinoma
avelumab
cisplatin-ineligible
induction immunotherapy
fi rst-line therapy
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spelling 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 studyRodriguez-Vida, AValderrama, BPCastellano, DPinto, AMellado, BPuente, JCliment, MADomenech, MVazquez, FPerez-Gracia, JLBonfill, TMorales-Barrera, RGonzalez-Billalabeitia, EGarcia-del-Muro, XMaroto, PNavarro-Gorro, NJuanpere, NJuan, OBellmunt, Jmetastatic urothelial carcinomaavelumabcisplatin-ineligibleinduction immunotherapyfi rst-line therapyBackground: 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.ELSEVIER2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/17699ESMO OpenISSN: 20597029reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p176992026-06-11T12:45:17Z
dc.title.none.fl_str_mv 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
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
spellingShingle 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, A
metastatic urothelial carcinoma
avelumab
cisplatin-ineligible
induction immunotherapy
fi rst-line therapy
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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.creator.none.fl_str_mv 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
author Rodriguez-Vida, A
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv metastatic urothelial carcinoma
avelumab
cisplatin-ineligible
induction immunotherapy
fi rst-line therapy
topic metastatic urothelial carcinoma
avelumab
cisplatin-ineligible
induction immunotherapy
fi rst-line therapy
description 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.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fisabio.portalinvestigacion.com/publicaciones/17699
url https://fisabio.portalinvestigacion.com/publicaciones/17699
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv ELSEVIER
publisher.none.fl_str_mv ELSEVIER
dc.source.none.fl_str_mv ESMO Open
ISSN: 20597029
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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