Metformin may not improve survival in pancreatic cancer
PHILADELPHIA — The diabetes drug metformin was not associated with improved survival outcomes for patients with pancreatic cancer, according to retrospective study data presented at the American Association for Cancer Research Annual Meeting.
Metformin is being tested in cancer trials — more than 20 of which remain open — because epidemiologic studies have suggested that its use is associated with a reduction in cancer deaths.
However, Roongruedee Chaiteerakij, MD, PhD, of the division of gastroenterology and hepatology at the Mayo Clinic Cancer Center in Rochester, Minnesota, and colleagues identified inconsistencies and design flaws in many of these trials. Thus, Chaiteerakij and colleagues sought to evaluate metformin use and survival of patients with pancreatic ductal adenocarcinoma and address potential biases that are often part of retrospective clinical trials.
“Epidemiologic studies of medication exposure and cancer survival warrant very careful and detailed data collection and analysis to minimize biases,” Chaiteerakij said during a press conference. “Researchers should exercise caution when initiating clinical trials based on retrospective epidemiologic studies.”
The researchers identified 1,360 patients with pancreatic ductal adenocarcinoma and diabetes from the Mayo Clinic’s Specialized Programs of Research Excellence (SPORE) in pancreatic cancer database who were treated between 2000 and 2011.
OS was the primary outcome of the study.
Patients were categorized into five groups based on whether they had never used metformin (n = 908; reference group) or whether they started metformin more than 1 year before pancreatic cancer diagnosis (n = 84), within 1 year before pancreatic cancer diagnosis (n = 212), within 30 days after pancreatic cancer diagnosis (n = 104), or more than 30 days after pancreatic cancer diagnosis (n = 34).
The median survival for those patients who did not use metformin was 308 days compared with 292 days for those who had some metformin exposure.
Among 413 patients with resectable disease, those who used metformin demonstrated prolonged survival (median, 782 days) compared with those who did not use metformin (median, 612 days; P = .07). However, patients who started metformin more than 30 days after diagnosis had a median survival of 818 days, approximately 3.5 times longer than the median survival of any of the other groups that used metformin, which researchers noted skewed the survival data.
None of the other metformin use groups had a median survival as long as the never-users of the drug, and there was no statistical survival difference.
“These patients already survived more than 30 days, suggesting that there is an inherent survival bias in this group of patients,” Chaiteerakij said in a press release. “After accounting for these unintended biases, the benefit of metformin was not confirmed in our study.”
When compared with never-users, those who started metformin more than 1 year before diagnosis had an HR of 1.08 (95% CI, 0.85-1.37). Researchers calculated an HR of 0.99 (95% CI, 0.85-1.17) for those who started metformin within 1 year before diagnosis 1.04 (95% CI, 0.83-1.31) for those who started metformin within 30 days after diagnosis and 0.49 (95% CI, 0.33-0.74) for those who started metformin more than 30 days after diagnosis.
Chaiteerakij said that an analysis adjusted for several factors including BMI, gender, age and state of disease demonstrated no association between metformin use and survival.
“When we looked at most of the retrospective studies when they showed the benefit of metformin use in cancer survival, most of them classified the use of metformin as ‘ever’ and ‘never’ and most of them looked at metformin exposure prior to metformin use before diagnosis of any cancer,” Chaiteerakij said. “In reality, when you decide to do a clinical trial, you start the patient from the cancer diagnosis and put the patient on the drug. So, the study data doesn’t always match in the retrospective cohort.” – by Anthony SanFilippo
Disclosure: Chaiteerakij reported no relevant financial disclosures. HemOnc Today was unable to obtain a list of relevant disclosures for the other researchers.