Impact Of Metformin On Survival In Lung Cancer Patients

ObjectiveThis study aims to explore the impact of metformin on effect of lung cancer and the correlation between metformin and prognosis of lung cancer.MethodsSix databases including Pub Med,Embase,Cochrane Library,Wiley,Science Direct and Springer Link were thoroughly searched to identify the studies involving the correlation between metformin and prognosis of lung cancer.All statistical analyses were performed with Review Manager 5.3 software.Hazard ratio(HR)and 95%confidence interval(95%CI)was used as effect measures for survival analysis of lung cancer.The pooled relative risk(RR)and 95%CI was calculated to assess objective response rate(ORR),disease control rate(DCR)and safety.And a random effect model or fixed effect model was employed to calculate the pooled effect measures determined by Cochrane Q and I~2 statistic tests.Furthermore,stratified analysis was conducted to assess the sources of heterogeneity,and stability of the results was judged by eliminating the studies one by one.Publication bias was evaluated via a funnel plot.ResultsIn total,19 studies encompassing 10655 patients were included in this meta-analysis,consisting of 15 observational studies and 4 randomized controlled trials(RCTs).1.Correlation between metformin and survival in lung cancerIn observational studies,metformin improved the progression free survival(PFS)(HR=0.68,95%CI:0.49-0.94,P=0.02),disease free survival(DFS)(HR=0.63,95%CI:0.51-0.79,P<0.0001)and overall survival(OS)(HR=0.79,95%CI:0.70-0.88,P<0.0001)in lung cancer patients with diabetes.Further stratified analysis on region,lung cancer subtype and stage showed that OS of metformin group was prolonged in Asian region,non-Asian region,non-small cell lung cancer(NSCLC),small cell lung cancer(SCLC)and advanced NSCLC.However,no significant improvement in OS was observed in patients with non-divided subtype of lung cancer or locally advanced NSCLC.In the RCTs,metformin could not benefit PFS(HR=0.62,95%CI:0.31-1.25,P=0.18)and OS(HR=0.61,95%CI:0.31-1.18,P=0.14).Stratified analysis based on treatment strategy and daily dose of metformin showed that a favorable survival outcome occurred in the patients treated with platinum-based chemotherapy or low-dose of metformin(<2000mg/daily).However,there was no survival benefit existed in the patients treated with EGFR tyrosine kinase inhibitor(TKI)or high-dose of metformin(2000mg/daily).2.Correlation between metformin and anti-cancer efficacy and safety analysisThere was no remarkable distinction in ORR(RR=1.21,95%CI:0.89-1.64,P=0.22)and DCR(RR=1.03,95%CI:0.99-1.07,P=0.14)between metformin group and non-metformin group.Moreover,in the safety analysis on metformin combined with conventional anticancer treatment,there was no evident discrepancy of adverse effects between metformin group and non-metformin group.ConclusionsMetformin can improve OS,PFS and DFS in lung cancer patients with diabetes.However,in lung cancer patients without diabetes,only metformin plus platinum-based chemotherapy or low-dose metformin combined with conventional anticancer treatment can improve OS;besides,metformin combined with conventional anticancer treatment does not increase adverse effects.