Does metformin use effect overall survival for patients with pancreatic cancer?

Abstract

660 Background: In Canada, the incidence of pancreatic cancer ranks 11th amongst all cancers but has resulted in the third highest mortality. Despite advancements in both diagnostics and therapeutics, the 5-year overall survival rate of pancreatic adenocarcinoma (PDAC) remains under 10%. Emerging studies have begun to examine the role of the hypoglycemic medication metformin, in improving outcomes of patients with PDAC. In cell cultures, metformin has been shown to have direct growth-inhibitory actions on malignant cells, and previous retrospective studies have suggested a potential association between metformin use and increased overall survival in breast and prostate cancer. To identify if metformin plays a role in improving PDAC outcomes, we have conducted a retrospective review of PDAC in Nova Scotia, Canada. Methods: We conduced a retrospective study of 630 patients diagnosed with PDAC treated at the Halifax Infirmary (Halifax, Nova Scotia). Records of patients were reviewed and information regarding patient demographics, cancer staging, metformin use, date of diagnosis, and date of death were collected. Statistical analysis using the log rank method was done to determine if there was a statistically significant difference in overall survival between groups. Results: Among the 630 patients identified, there were 337 males and 293 females. The average age at time of diagnosis was 74.02 years. There was no significant difference found in overall survival of patients on metformin (n=132, mean overall survival (mOS) 6.68 months), compared to those not on metformin (n=498, average survival 7.44 months), p=0.989. Further subgroup analysis based on cancer staging showed that patients with resectable pancreatic cancer (AJCC stage I-IIA, n=140), who did not use metformin (n=106) had a mOS of 12.98 months compared to 9.71 months for metformin users (n=34), p=0.438. For patients with locally advanced disease (AJCC stage IIB-III, n=125), the average mOS of non-metformin users (n=103) was 11.10 months compared to 10.73 months for metformin users (n=22), p=0.803. For patients with metastatic disease (AJCC stage IV, n=365), the average survival of non-metformin users (n=289) was 3.48 months compared to 4.26 months for metformin users (n=76), p=0.803. Diabetic patients (n=195) on metformin (n=132) compared to those not on metformin (n=63), did not show significant survival difference (mOS 6.68 months vs 6.61 months respectively, p =0.602). Conclusions: Despite suggestion that metformin use may improve survival in some cancers, we found no statistical improvement in mOS for metformin use in PDAC patients. Future research including a prospective study should be undertaken to confirm these results in a larger sample size.