A Phase II Study of Allogeneic GM-CSF-Transfected Pancreatic Tumor Vaccine (GVAX) with Ipilimumab as Maintenance Treatment for Metastatic Pancreatic Cancer.
Clin Cancer Res
; 26(19): 5129-5139, 2020 10 01.
Article
en En
| MEDLINE
| ID: mdl-32591464
ABSTRACT
PURPOSE:
This phase II study tested granulocyte-macrophage colony-stimulating factor (GM-CSF)-allogeneic pancreatic tumor cells (GVAX) and ipilimumab in metastatic pancreatic ductal adenocarcinoma (PDA) in the maintenance setting. PATIENTS ANDMETHODS:
Patients with PDA who were treated with front-line chemotherapy consisting of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) in the metastatic setting and had ongoing response or stable disease after 8-12 doses were eligible. Patients were randomized 11 to treatment with GVAX and ipilimumab given every 3 weeks for four doses then every 8 weeks (Arm A) or to FOLFIRINOX continuation (Arm B). The primary objective was to compare overall survival (OS) between the two arms.RESULTS:
Eighty-two patients were included in the final analysis (Arm A 40; Arm B 42). The study was stopped for futility after interim analysis. Median OS was 9.38 months [95% confidence interval (CI), 5.0-12.2] for Arm A and 14.7 months (95% CI, 11.6-20.0) for Arm B (HR, 1.75; P = 0.019). Using immune-related response criteria, two partial responses (5.7%) were observed in Arm A and four (13.8%) in Arm B. GVAX + ipilimumab promoted T-cell differentiation into effector memory phenotypes both in the periphery and in the tumor microenvironment and increased M1 macrophages in the tumor.CONCLUSIONS:
GVAX and ipilimumab maintenance therapy did not improve OS over continuation of chemotherapy and resulted in a numerically inferior survival in metastatic PDA. However, clinical responses and biological effects on immune cells were observed. Further study of novel combinations in the maintenance treatment of metastatic PDA is feasible.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
/
Adenocarcinoma
/
Factor Estimulante de Colonias de Granulocitos y Macrófagos
/
Microambiente Tumoral
Tipo de estudio:
Clinical_trials
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2020
Tipo del documento:
Article