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.

Department of Clinical Pharmacology and Chemotherapy Russian Cancer Research Center Moscow Russia

Department of Gastroenterology Erasme University Hospital Brussels Belgium

Department of Gastroenterology Kanagawa Cancer Center Yokohama Japan

Department of Haematology Oncology and Internal Medicine Medical University of Warsaw Warsaw Poland

Department of Hematology Oncology and Tumor Immunology Charité University Berlin Germany

Department of Hepatobiliary and Pancreatic Oncology National Cancer Center Hospital East Kashiwa Japan

Department of Hepatobiliary and Pancreatic Oncology National Cancer Center Hospital Tokyo Japan

Department of Medical Oncology Solid Tumor Oncology Dana Farber Cancer Institute Boston USA

Department of Oncology Antwerp University Hospital Edegum Belgium

Department of Oncology Masaryk University Medical School and Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Oncology Military Institute of Health Services Warsaw Poland

Department of Oncology Palacký University Medical School and Teaching Hospital Olomouc

Department of Oncology St László Hospital Budapest Hungary

Development Oncology Therapeutics Amgen Inc Thousand Oaks USA

Digestive Oncology University Hospitals Gasthuisberg Leuven and KU Leuven Leuven Belgium

Global Biostatistical Science Amgen Ltd Cambridge UK

Global Development Thousand Oaks

Medical Oncology Department University Hospital Ramon y Cajal Madrid Spain

Medical Oncology Royal Melbourne Hospital Parkville VIC Australia

Medical Sciences Amgen Inc Thousand Oaks USA

Oncology Service Hospital de Clinicas de Porto Alegre Porto Alegre Brazil

Princess Margaret Cancer Centre University of Toronto Toronto ON Canada

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ClinicalTrials.gov
NCT01231347