Study findings suggested that there is no benefit in administering metformin after patients are diagnosed with pancreatic ductal adenocarcinoma (PDAC), according to an article published in the Journal of Clinical Oncology.1
Including metformin in the treatment arms of cancer clinical trials is based on survival benefit demonstrated in retrospective epidemiologic studies. However, unintended biases may exist when an analysis is performed using a conventional Cox proportional hazards regression model with dichotomous ever/never categorization.
Investigators sought to examine the impact of metformin exposure definitions, analytical methods, and patient selection on the estimated effect size of metformin exposure on survival in a large cohort of patients with PDAC.
A total of 980 patients were retrospectively included in the study and metformin exposure was documented. Median survival was assessed by Kaplan-Meier and log-rank methods. Hazard ratios and 95% confidence intervals were computed to compare time-varying covariate analysis with conventional Cox proportional hazard regression analysis.
Results showed that median survival of metformin users vs nonusers was 9.9 vs 8.9 months, respectively. By the time-varying covariate analysis, metformin use was not statistically significant with improved survival.
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No evidence was found regarding the benefit of metformin in the subset of patients who were metformin-naïve at the time of diagnosis. When analysis was performed by using the conventional Cox method, however, an artificial survival benefit of metformin was found, which pointed to biased results.
“We highlight the importance of patient selection and appropriate statistical analytical methods when studying medication exposure and cancer survival,” the authors concluded.
- Chaiteerakij R, Petersen GM, Bamlet WR, et al. Metformin use and survival of patients with pancreatic cancer: a cautionary lesson [published online ahead of print April 11, 2016]. J Clin Oncol. doi: 10.1200/JCO.2015.63.3511.