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

Ann Oncol. 2015 May;26(5):921-927. doi: 10.1093/annonc/mdv027. Epub 2015 Jan 21.

Abstract

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.

Keywords: IGF-1 receptor; biomarker; ganitumab; gemcitabine; pancreatic cancer.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Administration, Intravenous
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / blood
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Disease Progression
  • Disease-Free Survival
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Proportional Hazards Models
  • Time Factors
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor
  • Deoxycytidine
  • gemcitabine
  • ganitumab

Associated data

  • ClinicalTrials.gov/NCT01231347