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 |
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| Affiliation: | 1. Department of Medical Oncology/Solid Tumor Oncology, Dana-Farber Cancer Institute, Boston, USA;2. Oncology Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil;3. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan;4. Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium;5. Medical Oncology, Royal Melbourne Hospital, Parkville, VIC, Australia;6. Department of Hematology, Oncology, and Tumor Immunology, Charité University, Berlin, Germany;7. Department of Oncology, Military Institute of Health Services, Warsaw, Poland;8. Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada;9. Department of Oncology, Antwerp University Hospital, Edegum, Belgium;10. Department of Oncology, St László Hospital, Budapest, Hungary;11. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan;12. Department of Oncology, Palacký University Medical School and Teaching Hospital, Olomouc;13. Department of Oncology, Masaryk University Medical School and Masaryk Memorial Cancer Institute, Brno, Czech Republic;14. Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan;15. Department of Haematology, Oncology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland;16. Department of Clinical Pharmacology and Chemotherapy, Russian Cancer Research Center, Moscow, Russia;17. Digestive Oncology, University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium;18. Medical Sciences, Amgen Inc., Thousand Oaks, USA;19. Global Biostatistical Science, Amgen Ltd, Cambridge, UK;20. Global Development, Thousand Oaks;21. Development Oncology Therapeutics, Amgen Inc., Thousand Oaks, USA;22. Medical Oncology Department, University Hospital Ramon y Cajal, Madrid, Spain |
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| Abstract: | This double-blind, phase 3 study assessed the efficacy and safety of ganitumab plus gemcitabine as first-line treatment of metastatic pancreatic cancer. The study was stopped after a preplanned futility analysis indicated a positive outcome was unlikely at primary analysis. Ganitumab plus gemcitabine had manageable toxicity but did not improve OS versus gemcitabine alone in unselected patients.BackgroundThis 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 methodsPatients 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 end point was overall survival (OS). Secondary end points included progression-free survival (PFS), safety, and efficacy by levels of circulating biomarkers.ResultsOverall, 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.ConclusionGanitumab combined with gemcitabine had manageable toxicity but did not improve OS, compared with gemcitabine alone in unselected patients with metastatic pancreatic cancer.Clinical trial registrationClinicalTrials.gov NCT01231347. |
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