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Abstract

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 † C. S. Fuchs 1 * , S. Azevedo 2 , T. Okusaka 3 , J.-L. Van Background: This double-blind, phase 3 study assessed the efficacy and safety of ganitumab combined with gemcitabine as first-line treatment of 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/m 2 (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 end point was overall survival (OS). Secondary end points 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 preplanned futility analysis; the final results are reported. Median OS was 7.2 months [95% confidence interval (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 [hazard ratio (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, 3.6 (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 [insulin-like growth factor-1 (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. Clinical trial registration: ClinicalTrials.gov NCT01231347