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.
Level 2 - randomized trial
Phase 3 randomized, double-blind, placebo-controlled trial
PubMed 25609246 · doi:10.1093/annonc/mdv027
What was done
A phase 3, double-blind, placebo-controlled trial evaluated the efficacy and safety of adding ganitumab to gemcitabine as first-line therapy for metastatic pancreatic adenocarcinoma. A total of 800 patients were randomly assigned 2:2:1 to receive intravenous gemcitabine (1000 mg/m2 on days 1, 8, and 15 of 28-day cycles) with placebo (n = 322), ganitumab 12 mg/kg (n = 318), or ganitumab 20 mg/kg (n = 160; days 1 and 15 of each cycle). The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), safety, and circulating biomarker analyses (IGF-1, IGFBP-2, IGFBP-3).
What was found
The study was stopped early based on a preplanned futility analysis. Median OS was 7.2 months (95% CI, 6.3-8.2) in the placebo group, 7.0 months (95% CI, 6.2-8.5) in the ganitumab 12-mg/kg group (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 group (HR 0.97; 95% CI, 0.76-1.23; P = 0.397). Median PFS was 3.7 months for placebo, 3.6 months for ganitumab 12 mg/kg (HR 1.00; 95% CI, 0.84-1.20; P = 0.520), and 3.7 months for ganitumab 20 mg/kg (HR 0.97; 95% CI, 0.77-1.22; P = 0.403). No unexpected toxicity was observed. Assessed circulating biomarkers showed no association with treatment effect on OS or PFS.
Why it matters
This phase 3 trial demonstrates that targeting IGF-1 receptor signaling with ganitumab combined with gemcitabine does not improve survival outcomes over gemcitabine alone in metastatic pancreatic cancer.
Limits
The study tested an unselected population, and evaluated circulating biomarkers failed to identify a predictive subgroup. Detailed numeric toxicity and adverse event rates are not provided in the abstract.
Cited by
- supports Amgen conducted a Phase 2 trial of an IGF receptor antibody in advanced pancreatic cancer that failed despite reducing IGF levels at the receptor by 50%, and the antibody does not cross the blood-brain barrier.