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

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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Detalles Bibliográficos
Autores: Rodriguez-Vida, Alejo|||0000-0002-7304-6857, Pérez Valderrama, Begoña|||0000-0003-0175-1263, Castellano, Daniel|||0000-0002-9106-0687, Pinto Marín, Álvaro|||0000-0002-4719-053X, Mellado, Begoña|||0000-0002-8088-5966, Puente, J.|||0000-0002-6910-1331, Climent, Miguel Ángel|||0000-0001-7523-0212, Domènech, Montserrat|||0000-0003-3973-0986, Vazquez Vázquez, Francisco|||0000-0002-0279-2414, Perez-Gracia, José Luis|||0000-0003-4941-9075, Bonfill Abella, Teresa|||0000-0003-2775-0293, Morales-Barrera, Rafael|||0000-0001-7398-0685, Gonzalez-Billalabeitia, Enrique|||0000-0003-3143-3143, Garcia del Muro, Xavier|||0000-0001-5571-2847, Maroto Rey, Pablo|||0000-0002-0030-0412, Navarro Gorro, Nil|||0000-0003-4633-9205, Juanpere, Nuria|||0000-0003-4954-9494, Juan, Óscar|||0000-0002-7772-9030, Bellmunt, Joaquim|||0000-0003-2328-3421
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:301272
Acceso en línea:https://ddd.uab.cat/record/301272
https://dx.doi.org/urn:doi:10.1016/j.esmoop.2024.103690
Access Level:acceso abierto
Palabra clave:Avelumab
Cisplatin-ineligible
First-line therapy
Induction immunotherapy
Metastatic urothelial carcinoma
Descripción
Sumario: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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