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
; 9(9): 103690, 2024 Sep.
Article
de En
| MEDLINE
| ID: mdl-39214051
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 ANDMETHODS:
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.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Protocoles de polychimiothérapie antinéoplasique
/
Anticorps monoclonaux humanisés
Limites:
Aged
/
Aged80
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Female
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Humans
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Male
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Middle aged
Langue:
En
Journal:
ESMO Open
/
ESMO open
Année:
2024
Type de document:
Article
Pays de publication:
Royaume-Uni