biostudies-literatureUnknown10(3)Han R<h4>Background</h4>Resistance is almost inevitable and is still a major obstacle in epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy. Only limited relevant clinical studies evaluated the therapeutic effects by combing metformin and EGFR-TKIs in non-small cell lung cancer (NSCLC) patients. Therefore, we evaluated the efficacy of concurrent use of metformin with EGFR-TKIs, and assessed whether the addition of metformin may improve clinical outcomes and delay the occurrence of EGFR-TKI resistance.<h4>Methods</h4>We conducted cell proliferation and apoptosis assay for investigation of metformin in combination with EGFR-TKIs to overcome EGFR-TKI resistance <i>in vitro</i>. Furthermore, we retrospectively reviewed clinicopathological characteristics and therapeutic outcomes of EGFR-mutant advanced NSCLC diabetic patients who received EGFR-TKIs with or without concurrent use of metformin.<h4>Results</h4><i>In vitro</i> experiment, metformin showed synergistic interaction both with gefitinib in PC9R (CI =0.77) and with osimertinib in PC9R/OR (CI =0.77) in proliferation inhibition assay. Metformin can also augment apoptosis effect of these TKI-resistant cells to EGFR-TKIs. In retrospective cohort, a total of 85 patients were identified (cohort A), in which 28 patients had concurrent use of metformin. The objective response rate in metformin use group was significantly higher (85.7% <i>vs.</i> 47.4%, P=0.001). The median progression-free survival (PFS) and overall survival (OS) in metformin use group were significantly longer (21.6 <i>vs.</i> 9.2 months, P=0.000; 48.4 <i>vs.</i> 36.6 months, P=0.049). Further analysis revealed that metformin obviously prolonged the median PFS2 of osimertinib treatment among patients who progressed to prior line EGFR-TKIs due to secondary EGFR T790M mutation (cohort B).<h4>Conclusions</h4>Our study suggest that concurrent use of metformin could be beneficial to EGFR-mutant NSCLC patients treated with either first-line EGFR-TKIs or second-line osimertinib.Translational lung cancer research1277-1291https://www.ebi.ac.uk/biostudies/studies/S-EPMC8044488biostudies-literatureConcurrent use of metformin enhances the efficacy of EGFR-TKIs in patients with advanced EGFR-mutant non-small cell lung cancer-an option for overcoming EGFR-TKI resistance.PMC8044488Han RLi JZhao CLiu SZhang QChen DLiu XLi XLiu YZhao SZhou CJia YShi JfalseConcurrent use of metformin enhances the efficacy of EGFR-TKIs in patients with advanced EGFR-mutant non-small cell lung cancer-an option for overcoming EGFR-TKI resistance.<h4>Background</h4>Resistance is almost inevitable and is still a major obstacle in epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy. Only limited relevant clinical studies evaluated the therapeutic effects by combing metformin and EGFR-TKIs in non-small cell lung cancer (NSCLC) patients. Therefore, we evaluated the efficacy of concurrent use of metformin with EGFR-TKIs, and assessed whether the addition of metformin may improve clinical outcomes and delay the occurrence of EGFR-TKI resistance.<h4>Methods</h4>We conducted cell proliferation and apoptosis assay for investigation of metformin in combination with EGFR-TKIs to overcome EGFR-TKI resistance <i>in vitro</i>. Furthermore, we retrospectively reviewed clinicopathological characteristics and therapeutic outcomes of EGFR-mutant advanced NSCLC diabetic patients who received EGFR-TKIs with or without concurrent use of metformin.<h4>Results</h4><i>In vitro</i> experiment, metformin showed synergistic interaction both with gefitinib in PC9R (CI =0.77) and with osimertinib in PC9R/OR (CI =0.77) in proliferation inhibition assay. Metformin can also augment apoptosis effect of these TKI-resistant cells to EGFR-TKIs. In retrospective cohort, a total of 85 patients were identified (cohort A), in which 28 patients had concurrent use of metformin. The objective response rate in metformin use group was significantly higher (85.7% <i>vs.</i> 47.4%, P=0.001). The median progression-free survival (PFS) and overall survival (OS) in metformin use group were significantly longer (21.6 <i>vs.</i> 9.2 months, P=0.000; 48.4 <i>vs.</i> 36.6 months, P=0.049). Further analysis revealed that metformin obviously prolonged the median PFS2 of osimertinib treatment among patients who progressed to prior line EGFR-TKIs due to secondary EGFR T790M mutation (cohort B).<h4>Conclusions</h4>Our study suggest that concurrent use of metformin could be beneficial to EGFR-mutant NSCLC patients treated with either first-line EGFR-TKIs or second-line osimertinib.2021-01-01T00:00:00Z2021 Mar2025-04-27T00:10:02.438Z2025-04-06T17:46:48.64ZS-EPMC80444883388950910.21037/tlcr-20-1153