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Dutch Study Indicates No Survival Benefit of Adding Metformin to Gemcitabine-Erlotinib in Advanced Pancreatic Cancer

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Key Points

  • No significant difference in 6-month overall survival was observed with the addition of metformin to gemcitabine-erlotinib in patients with advanced pancreatic cancer.
  • No difference in median overall survival was observed.

In a Dutch phase II study reported in The Lancet Oncology, Kordes et al found that adding metformin to gemcitabine-erlotinib (Tarceva) did not improve overall survival in patients with advanced pancreatic cancer.

Study Details

In the double-blind study, 121 patients from four centers in the Netherlands were randomly assigned between May 2010 and January 2014 to receive intravenous gemcitabine 1,000 mg/m² on days 1, 8, and 15 every 4 weeks and oral erlotinib 100 mg once daily with placebo (n = 61) or metformin (n = 60). The metformin dose was increased from 500 mg (first week) to 1,000 mg twice daily. The primary endpoint was overall survival at 6 months.

Metformin and placebo patients had a median age of 64 and 65 years, 57% and 44% were male, 73% and 74% had metastatic disease, 82% and 93% had a World Health Organization performance status of 0 or 1, and study treatment was first-line in 97% in both groups.

Survival

Overall survival at 6 months was 56.7% (95% confidence interval [CI] = 44.1%–69.2%) in the metformin group and 63.9% (95% CI = 51.9%–75.9%) in the placebo group (P = .41). Median overall survival was 6.8 months (95% CI = 5.1–8.5 months) in the metformin group vs 7.6 months (95% CI = 6.1–9.1 months) in the placebo group (hazard ratio = 1.056, P = .78).

The most common grade 3 or 4 adverse events were neutropenia (25% in the metformin group vs 25% in the placebo group), skin rash (7% vs 10%), diarrhea (10% vs 5%), and fatigue (10% vs 3%).

The investigators concluded: “Addition of a conventional anti-diabetic dose of metformin does not improve outcome in patients with advanced pancreatic cancer treated with gemcitabine and erlotinib. Future research should include studies of more potent biguanides and should focus on patients with hyperinsulinaemia and patients with tumours showing markers of sensitivity to energetic stress, such as loss of function of AMP kinase, a key regulator of cellular energy homoeostasis.”

Johanna W. Wilmink, MD, of the Academic Medical Centre, Amsterdam, is the corresponding author of The Lancet Oncology article.

The study was funded by the Academic Medical Centre, Amsterdam, and The Terry Fox Foundation, Vancouver, Canada.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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