Han Rui, Li Jianghua, Wang Yubo, He Tingting, Zheng Jie, He Yong
Department of Respiratory Disease, Daping Hospital, Army Medical University, Chongqing 400042, China.
Chin Med J Pulm Crit Care Med. 2023 Jun 17;1(2):119-124. doi: 10.1016/j.pccm.2023.04.006. eCollection 2023 Jun.
The synergistic association between metformin and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has been confirmed in 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 investigate whether BMI is associated with the synergistic effect of metformin and EGFR-TKIs in advanced mutation (m)-positive non-small cell lung cancer (NSCLC) among nondiabetic Asian population.
We performed a 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 m NSCLC. We stratified patients into those with a high BMI (≥24 kg/m) and those with a low BMI (<24 kg/m) 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.
In the univariate analysis, patients who had a high BMI ( = 56) in the gefitinib + metformin group ( = 28) did not have a better PFS (8.84 months 11.67 months; = 0.351) or OS (15.58 months 24.36 months; = 0.095) than those in the gefitinib + placebo group ( = 28). Similar results were also observed in the low-BMI groups. Strikingly, in the metformin plus gefitinib group, patients who had low BMI ( = 69) showed significantly better OS than those with high BMI (24.89 months [95% CI, 20.68 months-not reached] 15.58 months [95% CI, 13.78-31.53 months]; = 0.007), but this difference was not observed in PFS (10.78 months . 8.84 months; = 0.285).
Our study showed that nondiabetic Asian advanced NSCLC patients with mutations who have low BMI seem to get better OS from metformin plus EGFR-TKI treatment.
二甲双胍与表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKIs）之间的协同关联已在研究中得到证实。哪些患者能从二甲双胍联合EGFR-TKIs治疗中获益仍存在争议。体重指数（BMI）被证明与无进展生存期（PFS）延长和总生存期（OS）独立相关。本研究旨在调查在非糖尿病亚洲人群中，BMI是否与二甲双胍和EGFR-TKIs在晚期表皮生长因子受体基因突变（m）阳性非小细胞肺癌（NSCLC）中的协同效应相关。
我们对一项前瞻性、双盲II期随机临床试验（COAST，NCT01864681）进行了分析，该试验纳入了224例未经治疗的IIIB-IV期mNSCLC非糖尿病患者。我们将患者分为高BMI（≥24kg/m²）组和低BMI（<24kg/m²）组，以分析两组之间PFS和OS的差异。使用Kaplan-Meier曲线分析PFS和OS，并使用对数秩检验比较组间差异。
在单因素分析中，吉非替尼+二甲双胍组（n = 28）中高BMI（n = 56）的患者与吉非替尼+安慰剂组（n = 28）的患者相比，PFS（8.84个月对11.67个月；P = 0.351）或OS（15.58个月对24.36个月；P = 0.095）并无改善。在低BMI组中也观察到了类似结果。令人惊讶的是，在二甲双胍加吉非替尼组中，低BMI（n = 69）的患者的OS明显优于高BMI患者（24.89个月[95%CI，20.68个月-未达到]对15.58个月[95%CI，13.78-31.53个月]；P = 0.007），但在PFS方面未观察到这种差异（10.78个月对8.84个月；P = 0.285）。
我们的研究表明，BMI低的非糖尿病亚洲晚期NSCLC患者在接受二甲双胍联合EGFR-TKI治疗时似乎能获得更好的OS。
