Author of

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  P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall

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    P3.01-70 - Meta-Analysis of Metformin in Combination with Platinum Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer (ID 12602)

    12:00 - 13:30  |  Author(s): Anish Parikh
    • Abstract
    • Slides

    Background
    

    Metformin has been shown to have a variety of insulin-dependent and –independent antitumor effects, primarily through cellular growth inhibition via the AMP-activated protein kinase (AMPK) pathway and the IGF1-insulin axis. Two prospective trials evaluating metformin with platinum doublet chemotherapy +/- bevacizumab have demonstrated competitive outcomes in non-diabetic, chemotherapy-naïve advanced non-small cell lung cancer (NSCLC) patients. Outcomes in KRAS-mutated NSCLC, an area of interest due to potential co-occurring LKB1 mutations, an AMPK pathway upstream kinase, is currently unknown.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    This meta-analysis is of two phase II study treatment arms (NCT02019979, NCT01578551), evaluating the use of concurrent metformin and platinum-based doublet chemotherapy +/- bevacizumab. Patient’s demographic, molecular and adverse event (AE) profiles were summarized with descriptive statistics. Kaplan-Meier curves for progression free survival (PFS) and overall survival (OS) were generated for all patients, as well as known KRAS and EGFR mutation subsets.

    4c3880bb027f159e801041b1021e88e8 Result
    

    33 non-squamous NSCLC patients were treated; 60% were female and the median age was 64 (Range: 37-77). The most common AE was neutropenia (Grade 3-4: 30%). No patients required study treatment cessation due to metformin-related toxicity. Across all patients, mPFS was 6 months (95% CI: 1.36-7.96); mOS was 14.83 months (95% CI: 8.25-19.99). In KRAS-mutated patients (n=13), mPFS was 7.21 months; mOS was 17.46 months. In EGFR-mutated patients (n=7), mPFS was 6.57 months; mOS was 13.25 months.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Combination metformin and chemotherapy +/- bevacizumab was safe and well-tolerated in advanced, chemotherapy-naïve non-squamous NSCLC across two phase II clinical trials. Metformin appeared particularly effective in KRAS-mutated NSCLC. Data for LKB1 status was unknown for a majority of patients, but may be an important co-mechanism for benefit. Metformin appeared to underperform in the EGFR subset, perhaps due to lack of TKI use. Given the tolerability, low cost and activity observed in NSCLC, further investigation into metformin’s antitumor effects in molecularly defined subsets is needed.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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