Author of

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  P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Targeted Therapy - Clinically Focused
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 36344

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    P76.07 - Metformin Enhances the Efficacy of EGFR-TKIs in Advanced Non-Small Cell Lung Cancer Patients With Type 2 Diabetes Mellitus (ID 897)

    00:00 - 00:00  |  Presenting Author(s): Ruoshuang Han
    • Abstract
    • Slides

    Introduction
    

    Lung cancer remains the leading cause of cancer-related mortality around the world. Despite epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) therapy have shown remarkable clinical efficacy in non-small cell lung cancer (NSCLC) patients, resistance is almost inevitable and is still a major obstacle. Studies have suggested that the prolonged use of metformin, a common oral anti-diabetes agent, also an IGF-1R inhibitor, is associated with survival benefits among NSCLC Type 2 diabetes mellitus (T2DM) patients. However, the clinical efficacy of metformin and EGFR-TKIs in combination, especially third-generation TKIs, on NSCLC patients with T790M mutation has not been well validated. Therefore, we retrospectively reviewed the effect of metformin use on the clinical efficacy of EGFR-TKIs in NSCLC patients with T2DM, and we also carried out in vitro experiment to demonstrate the effects of metformin in EGFR-TKI resistant cell lines in aspect of proliferation and apoptosis.

    Methods
    

    We retrospectively reviewed clinicopathological characteristics and response of NSCLC patients with type 2 diabetes mellitus (T2DM) who received EGFR-TKIs treatment. Therapeutic outcome including objective response rate (ORR), median progression-free survival (PFS) and overall survival (OS) of first-line EGFR-TKIs and second-line osimertinib were compare between patients received metformin and other anti-diabetes drugs. In addition, the effect of metformin on gefitinib-resistant cell line PC9R and osimertinib-resistant cell line PC9R/OR was examined in vitro using Cell Counting Kit-8, and apoptosis analysis, the IC _50, apoptosis rate and combination index (CI) was calculated.

    Results
    

    In fist-line EGFR-TKIs treatment, ORR in metformin use group was significantly higher (85.7% vs. 47.4%, p=0.001). The PFS1 and OS1 in metformin use group were significantly longer (21.6 months vs. 9.2 months, p =0.000; 48.4 months vs. 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 with T790M. In vitro analysis, metformin showed synergistic interaction both with gefitinib in PC9R (CI=0.77) and with osimertinib in PC9R/OR (CI=0.77) in proliferation inhibition analysis. Metformin can also augment apoptosis effect of these TKI-resistant cells to EGFR-TKIs in vitro (p<0.05).

    

    Conclusion
    

    The results of our study suggest metformin use could be beneficial to NSCLC patients with T2DM treated with either first-line EGFR-TKIs or second-line osimertinib treatment.

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