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
Por:
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
Publicada:
1 sep 2024
Resumen:
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.
Filiaciones:
Rodriguez-Vida, A:
Hosp Mar, Med Oncol Dept, CIBERONC, Barcelona, Spain
Valderrama, BP:
Hosp Univ Virgen Rocio, Med Oncol Dept, Seville, Spain
Castellano, D:
Hosp 12 Octubre, Med Oncol Dept, Madrid, Spain
Pinto, A:
Hosp La Paz, Med Oncol Dept, Madrid, Spain
Mellado, B:
Univ Barcelona, Hosp Clin, Med Oncol Dept, Lab Traslat Genom Solid Tumors,IDIBAPS, Barcelona, Spain
Puente, J:
Hosp Clin San Carlos, Inst Invest Sanitaria Hosp Clin San Carlos IdISSC, Med Oncol Dept, CIBERONC, Madrid, Spain
Climent, MA:
Inst Valenciano Oncol, Med Oncol Dept, Valencia, Spain
Domenech, M:
Hosp Althaia, Med Oncol Dept, Manresa, Spain
Vazquez, F:
Hosp Gen Univ Elche, Med Oncol Dept, Alicante, Spain
Perez-Gracia, JL:
Hosp Mar, Med Oncol Dept, CIBERONC, Barcelona, Spain
Clin Univ Navarra, Oncol Dept, Pamplona, Spain
Bonfill, T:
Hosp Univ Parc Tauli, Med Oncol Dept, Sabadell, Spain
Morales-Barrera, R:
Hosp Mar, Med Oncol Dept, CIBERONC, Barcelona, Spain
Hosp Univ Virgen Rocio, Med Oncol Dept, Seville, Spain
Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Med Oncol Dept, Barcelona, Spain
Gonzalez-Billalabeitia, E:
Hosp Mar, Med Oncol Dept, CIBERONC, Barcelona, Spain
Hosp 12 Octubre, Med Oncol Dept, Madrid, Spain
Hosp Morales Meseguer, Med Oncol Dept, Murcia, Spain
Garcia-del-Muro, X:
Hosp Mar, Med Oncol Dept, CIBERONC, Barcelona, Spain
Hosp La Paz, Med Oncol Dept, Madrid, Spain
Univ Barcelona, Inst Catala Oncol IDIBELL Res Inst, Med Oncol Dept, Barcelona, Spain
Maroto, P:
Hosp Mar, Med Oncol Dept, CIBERONC, Barcelona, Spain
Univ Barcelona, Hosp Clin, Med Oncol Dept, Lab Traslat Genom Solid Tumors,IDIBAPS, Barcelona, Spain
Hosp Santa Creu i St Pau, Med Oncol Dept, Barcelona, Spain
Navarro-Gorro, N:
Hosp Mar, Med Oncol Dept, CIBERONC, Barcelona, Spain
Juanpere, N:
Hosp Mar, Med Oncol Dept, CIBERONC, Barcelona, Spain
Hosp Clin San Carlos, Inst Invest Sanitaria Hosp Clin San Carlos IdISSC, Med Oncol Dept, CIBERONC, Madrid, Spain
Hosp Mar, IMIM Res Inst, Pathol Dept, Barcelona, Spain
Juan, O:
Hosp Mar, Med Oncol Dept, CIBERONC, Barcelona, Spain
Inst Valenciano Oncol, Med Oncol Dept, Valencia, Spain
Pivotal SLU Clin Res Org, Med Oncol, Madrid, Spain
Bellmunt, J:
Hosp Mar, Med Oncol Dept, CIBERONC, Barcelona, Spain
Harvard Med Sch, Dana Farber Canc Ctr, Brookline Ave,D-907, Boston, MA 02215 USA
Green Published, gold
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