Low BMI patients with advanced EGFR mutation-positive NSCLC can get a better outcome from metformin plus EGFR-TKI as first-line therapy:A secondary analysis of a phase 2 randomized clinical trial  

作　　者：Rui Han Jianghua Li Yubo Wang Tingting He Jie Zheng Yong He 

机构地区：[1]Department of Respiratory Disease,Daping Hospital,Army Medical University,Chongqing 400042,China

出　　处：《Chinese Medical Journal Pulmonary and Critical Care Medicine》2023年第2期119-124,共6页呼吸与危重症医学（英文）

基　　金：This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.81972189,82172623,81802293,and 81902343);Chongqing Science and Technology Commission(No.cstc2021jcyj-msxmX0014).

摘　　要：Background:The synergistic association between metformin and epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)has been confirmed in in vitro studies.It is still controversial which patients can benefit from metformin plus EGFR-TKIs treatment.Body mass index(BMI)was proved to be independently associated with prolonged progression-free survival(PFS)and overall survival(OS).This study aimed to in-vestigate whether BMI is associated with the synergistic effect of metformin and EGFR-TKIs in advanced EGFR mutation(EGFR m)-positive non-small cell lung cancer(NSCLC)among nondiabetic Asian population.Methods:We performed a post hoc analysis of a prospective,double-blind phase II randomized clinical trial(COAST,NCT01864681),which enrolled 224 patients without diabetes with treatment-naïve stage IIIB-IV EGFR m NSCLC.We stratified patients into those with a high BMI(≥24 kg/m^(2))and those with a low BMI(<24 kg/m^(2))to allow an analysis of the difference in PFS and OS between the two groups.The PFS and OS were analyzed using Kaplan-Meier curves,and the differences between groups were compared using log-rank test.Results:In the univariate analysis,patients who had a high BMI(n=56)in the gefitinib+metformin group(n=28)did not have a better PFS(8.84 months vs.11.67 months;P=0.351)or OS(15.58 months vs.24.36 months;P=0.095)than those in the gefitinib+placebo group(n=28).Similar results were also observed in the low-BMI groups.Strikingly,in the metformin plus gefitinib group,patients who had low BMI(n=69)showed significantly better OS than those with high BMI(24.89 months[95%CI,20.68 months-not reached]vs.15.58 months[95%CI,13.78-31.53 months];P=0.007),but this difference was not observed in PFS(10.78 months vs.8.84 months;P=0.285).Conclusions:Our study showed that nondiabetic Asian advanced NSCLC patients with EGFR mutations who have low BMI seem to get better OS from metformin plus EGFR-TKI treatment.

关 键 词：Non-small cell lung cancer METFORMIN Epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs) Body mass index GEFITINIB 

分 类 号：R734.2[医药卫生—肿瘤]