Phase 2 Placebo-Controlled, Double-Blind Trial of Dasatinib Added to Gemcitabine for Patients with Locally-Advanced Pancreatic Cancer
Mené sur des patients atteints d'un cancer du pancréas de stade localement avancé, cet essai de phase II évalue l'efficacité, du point de vue de la survie globale, et la toxicité de l'ajout du dasatinib à un traitement par gemcitabine
Background: Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate with limited treatment options. Gemcitabine provides a marginal survival benefit for patients with advanced PDAC. Dasatinib is a competitive inhibitor of Src kinase, which is overexpressed in PDAC tumors. Dasatinib and gemcitabine were combined in a phase 1 clinical trial where stable disease was achieved in 2 of 8 patients with gemcitabine-refractory PDAC. Patients and methods: This placebo-controlled, randomized, double-blind, phase II study compared the combination of gemcitabine plus dasatinib to gemcitabine plus placebo in patients with locally advanced, non-metastatic PDAC. Patients received gemcitabine 1,000 mg/m2 (30- minute IV infusion) on days 1, 8, 15 of a 28-day cycle combined with either 100 mg oral dasatinib or placebo tablets daily. The primary objective was overall survival (OS), with safety and progression-free survival (PFS) as secondary objectives. Exploratory endpoints included overall response rate, freedom from distant metastasis, pain and fatigue progression and response rate, and CA19-9 response rate. Results: There was no statistically significant difference in OS between the 2 treatment groups (HR = 1.16; 95% confidence interval [CI]: 0.81–1.65; p=0.5656). Secondary and exploratory endpoint analyses also showed no statistically significant differences. The burden of toxicity was higher on the dasatinib arm. Conclusions: Dasatinib failed to show increased OS or PFS in patients with locally advanced PDAC. Alternative combinations or trial designs may show a role for src inhibition in PDAC treatment.
Annals of Oncology 2016