A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Ganitumab or Placebo in Combination With Gemcitabine as First-Line Therapy for Metastatic Adenocarcinoma of the Pancreas: the GAMMA Trial
Mené sur 800 patients atteints d'un adénocarcinome métastatique du pancréas, cet essai de phase III évalue l'efficacité, du point de vue de la survie globale, et la toxicité du ganitumab en combinaison avec la gemcitabine
Background : This double-blind, phase 3 study assessed the efficacy and safety of ganitumab combined with gemcitabine as first-line treatment for metastatic pancreatic cancer. Patients and Methods : Patients with previously untreated metastatic pancreatic adenocarcinoma were randomly assigned 2:2:1 to receive intravenous gemcitabine 1000 mg/m2 (days 1, 8, and 15 of each 28-day cycle) plus placebo, ganitumab 12 mg/kg, or ganitumab 20 mg/kg (days 1 and 15 of each cycle). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), safety, and efficacy by levels of circulating biomarkers. Results : Overall, 322 patients were randomly assigned to placebo, 318 to ganitumab 12 mg/kg, and 160 to ganitumab 20 mg/kg. The study was stopped based on results from a pre-planned futility analysis; the final results are reported. Median OS was 7.2 months (95% CI, 6.3−8.2) in the placebo arm, 7.0 months (95% CI, 6.2−8.5) in the ganitumab 12-mg/kg arm (HR, 1.00; 95% CI, 0.82−1.21; P=0.494), and 7.1 months (95% CI, 6.4−8.5) in the ganitumab 20-mg/kg arm (HR, 0.97; 95% CI, 0.76−1.23; P=0.397). Median PFS was 3.7 months, 3.6 months (HR, 1.00; 95% CI, 0.84−1.20; P=0.520), and 3.7 months (HR, 0.97; 95% CI, 0.77−1.22; P=0.403), respectively. No unexpected toxicity was observed with ganitumab plus gemcitabine. The circulating biomarkers assessed (IGF-1, IGF binding protein-2, and -3) were not associated with a treatment effect on OS or PFS by ganitumab. Conclusion : Ganitumab combined with gemcitabine had manageable toxicity but did not improve OS compared with gemcitabine alone in unselected patients with metastatic pancreatic cancer.
Annals of Oncology 2015