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 (Hospital del Mar (Barcelona, Catalunya))
Pérez Valderrama, Begoña (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Castellano, Daniel (Hospital Universitario 12 de Octubre (Madrid))
Pinto Marín, Álvaro (Hospital Universitario La Paz (Madrid))
Mellado, Begoña (Hospital Clínic i Provincial de Barcelona)
Puente, J (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos)
Climent, Miguel Ángel (Fundació Institut Valencià d'Oncologia)
Domènech, Montserrat (Hospital Althaia)
Vazquez Vázquez, Francisco (Hospital General Universitario de Elche)
Perez-Gracia, José Luis (Clínica Universidad de Navarra)
Bonfill Abella, Teresa (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Morales-Barrera, Rafael (Hospital Universitari Vall d'Hebron)
Gonzalez-Billalabeitia, Enrique (Hospital General Universitario Morales Meseguer (Múrcia))
Garcia del Muro, Xavier (Institut d'Investigació Biomèdica de Bellvitge)
Maroto Rey, Pablo (Institut de Recerca Sant Pau)
Navarro Gorro, Nil (Hospital del Mar (Barcelona, Catalunya))
Juanpere, Nuria (Institut Hospital del Mar d'Investigacions Mèdiques)
Juan, Óscar (Clinical Research Organisation (Madrid))
Bellmunt, Joaquim (Hospital del Mar (Barcelona, Catalunya))
Universitat Autònoma de Barcelona. Departament de Medicina

Data:	2024
Resum:	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.
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Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Avelumab ; Cisplatin-ineligible ; First-line therapy ; Induction immunotherapy ; Metastatic urothelial carcinoma
Publicat a:	ESMO open, Vol. 9 Núm. 9 (september 2024) , p. 103690, ISSN 2059-7029

DOI: 10.1016/j.esmoop.2024.103690
PMID: 39214051

10 p, 399.1 KB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d’Investigació i Innovació Parc Taulí (I3PT)
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Recerca Sant Pau
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