Phase II Randomized, Double-Blind Study of mFOLFIRINOX plus Ramucirumab versus mFOLFIRINOX plus placebo in Advanced Pancreatic Cancer Patients (HCRN GI14-198)
Mené sur 82 patients atteints d'un cancer du pancréas de stade métastatique, cet essai multicentrique de phase II évalue l'efficacité, du point de vue de la survie sans progression à 9 mois, et la toxicité de l'ajout du ramucirumab à une chimiothérapie de première ligne de type mFOLFIRINOX
Background: Vascular endothelial growth factor receptor (VEGFR)-mediated signaling promotes angiogenesis and contributes to resistance to therapy in pancreatic ductal adenocarcinoma (PDAC). Ramucirumab (RAM) is a monoclonal antibody against VEGFR. Based on this preclinical data, we conducted a randomized phase II trial to compare progression free survival (PFS) between modified FOLFIRINOX with or without RAM in first line therapy for patients with metastatic PDAC. Methods: This phase II randomized, multi-center, placebo controlled, and double-blinded, trial randomly assigned patients with recurrent/metatstatic PDAC to either mFOLFIRINOX/RAM (Arm A) or mFOLFIRINOX/Placebo (Arm B). mFOLFIRINOX (oxaliplatin [85 mg/m2], irinotecan [165 mg/m2], fluorouracil [2400 mg/m2]) was received every 2 weeks, with or without ramucirumab (8mg/kg). The primary endpoint is PFS at 9 months, and the secondary endpoints include overall survival (OS), response rate and toxicity evaluation in both arms. Results: A total of 86 subjects were enrolled, 82 were eligible (42 in Arm A v. 40 in Arm B). The mean age were comparable (61.7 v. 63.0, respectively). Majority of the patients were White (N=69) and males (N=43). The median PFS was 5.6 compared to 6.7 months, for Arm A and B, respectively. At 9 months, the PFS rates were 25.1% and 35.0% for Arms A and B, respectively (p=0.322). The median OS in Arm A was 10.3 compared to 9.7 months for Arm B (p=0.094). The disease response rate for Arm A was 17.7% compared to Arm B of 22.6% and was not statistically significant. On the univariate and multivariate analysis, there was no difference in distribution between the 2 arms for age, gender, race and ethnicity. FOLFIRINOX/RAM combination was well tolerated. Patients in Arm A reported a slightly higher number of adverse events (AEs) compared to Arm B (589 v. 516). The most reported AE in either arm was diarrhea (29 vs 28), fatigue (25 v. 25), vomiting (24 v. 14), weight loss (23 v. 17), and abdominal pain (20 v. 15). Arm A has more SAEs than Arm B (43 v. 25, respectively), Sepsis was the most commonly reported in both arms (3 in each), vomiting (3 v. 2), diarrhea (3 v.1) and duodenal obstruction (3 v. 0). Conclusions: The addition of RAM to FOLFIRINOX did not significantly impact PFS or OS. FOLFIRINOX/RAM combination was well tolerated in the treatment of PCA. (Funded by Eli Lilly; ClinicalTrials.gov number, NCT02581215) Keywords