Obesity-specific improvement of lung cancer outcomes and immunotherapy efficacy with metformin
Abstract
BACKGROUND: Preclinical cancer studies ascribe promising anticancer properties to metformin. Yet, clinical findings vary, casting uncertainty on its therapeutic value for non-small cell lung cancer (NSCLC) patients. We hypothesized that metformin could benefit obese and overweight patients with NSCLC.
METHODS: We retrospectively analyzed 2 clinical cohorts and employed complementary mouse models to test our hypothesis. One cohort included NSCLC patients with overweight body mass index (≥25 kg/m2, n = 511) and nonoverweight body mass index (<25 kg/m2, n = 232) who underwent lobectomy, evaluating metformin's impact on clinical outcomes. Another cohort examined metformin's effect on progression-free survival after immune checkpoint inhibitors in overweight (n = 284) vs nonoverweight (n = 184) NSCLC patients. Metformin's effects on tumor progression, antitumor immunity, and immune checkpoint inhibitor response in obese and normal-weight mice were assessed with lung cancer models.
RESULTS: Metformin is associated with increased recurrence-free survival in overweight patients (hazard ratio [HR] = 0.47, 95% confidence interval [CI] = 0.24 to 0.94; P = .035) after lobectomy. It also corrected accelerated tumor growth in diet-induced obese mouse models in a lymphocyte-specific manner while reversing several mechanisms of immune suppression potentiated by obesity. Programmed cell death 1 blockade coupled with metformin was more effective at limiting tumor burden in obese mice and…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 511 participants or records.
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