The prognostic value of metformin for advanced non-small cell lung cancer: a systematic review and meta-analysis

Background: The prognostic value of Metformin for concurrent non-small cell lung cancer (NSCLC) has been controversial in previous individual studies and meta-analyses. In order to further investigate the value of this medication, we conducted a systematic review and meta-analysis for patients with advanced or inoperable NSCLC. Methods: We searched articles from PubMed, Scopus and Web of Science databases; the time interval was from the inception date of the databases to 1 September 2017. Inclusion criteria for eligible studies were: advanced or inoperable NSCLC; Metformin as an experimental group, and non-Metformin usage as a control group; progression-free survival (PFS) or overall survival (OS) as the outcome, with available hazard ratio (HR). Data synthesis was conducted based on the random-effect model. Results: From a total of 97 articles in databases, we included seven eligible studies. Among them, only one study compared Metformin usage and non-Metformin usage for NSCLC patients who didn't have diabetes mellitus (DM): no significant difference was found in either OS or PFS. The remaining six studies compared Metformin usage and non-Metformin usage for patients with concurrent NSCLC and DM: according to meta-analysis, significantly prolonged OS was found in Metformin usage rather than non-Metformin usage [pooled HR = 0.87 (0.77-0.99), P=0.04]; no significant difference was indicated in PFS [pooled HR = 0.85 (0.67-1.07), P=0.16]. In subgroup analysis, among patients with late-stage NSCLC and DM, significant difference was found, regardless of OS [pooled HR = 0.81 (0.70-0.94), P<0.01] or PFS [pooled HR = 0.71 (0.58-0.88), P < 0.01]. However, among patients with local advanced NSCLC and DM, there was no significant difference [OS: pooled HR = 1.05 (0.79-1.40), P=0.74; PFS: pooled HR = 0.94 (0.68-1.32), P=0.74]. Conclusions: The prognostic value of Metformin for concurrent late-stage NSCLC and DM was demonstrated. It deserves further confirmation and explanation.