Metformin may improve survival for advanced lung adenocarcinoma patients with higher BMI and taking EGFR-TKI therapy

1. The overall progression-free survival (PFS) was 10.54 years.

2. Patients with body mass weight (BMI) ≥ 24 derived greater survival benefit from metformin plus epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), compared to EGFR-TKIs only.

Evidence Rating Level: 2 (Good)

Study Rundown: Recently, metformin has been associated with reducing the mortality of various cancers. Due to its anti-tumour properties, there have been interests in evaluating whether metformin improves the efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatments in cancer patients. There have been several phase 2 trials with lack of consistent results due to variations of metformin doses used and the differences in patient demographics. Therefore, this post-hoc study of a phase 2 trial aimed to explore whether there is an association of body mass index (BMI) and the clinical benefits from metformin in patients with advanced lung adenocarcinoma receiving EGFR-TKIs. The improvement in progression-free survival (PFS) and overall survival (OS) from adding metformin to EGFR-TKIs was only seen in patients with BMI ≥ 24. Patients with BMI <24 did not show benefit for either PFS or OS. Limitations of the analyses include that this is a post hoc analysis, inability to include all patients from the initial trial that have incomplete data and the limited number of patients. Overall, this study demonstrated that BMI could be a key factor modulator of the effect of metformin and EGFR-TKIs for cancer therapy. However, further prospective investigation is required to confirm the association of BMI with metformin and EGFR-TKI synergy.

Click to read the study in JAMA Oncology

Relevant Reading: Effect of metformin plus tyrosine kinase inhibitors compared with tyrosine kinase inhibitors alone in patients with epidermal growth factor receptor-mutated lung adenocarcinoma: a phase 2 randomized clinical trial

In-Depth [randomized controlled trial]: This was a post hoc analysis of a phase II study and included patients with epidermal growth factor receptor (EGFR) variant-positive non-small-cell lung cancer (NSCLC). Patients were randomized to receive EGFR-tyrosine kinase inhibitor (TKI) only or EGFR-TKI plus metformin. A total of 133 patients (mean age [SD]: 59.39 [13.07]) were included in the analysis. The overall progression-free survival (PFS) was 10.54 (95% confidence interval [CI]: 8.92-12.17). Patients with body mass weight (BMI) ≥ 24 showed statistically significant improvement in PFS from adding metformin to their EGFR-TKIs (15.83 months [95% CI: 9.93-21.73]), compared to EGFR-TKIs only (8.34 [95% CI: 6.09-10.59 months]). The corresponding hazard ratio was 0.4 (95% CI: 0.2-0.7, p=0.03). BMI ≥ 24 patients also showed improvement to OS from the addition of metformin to their EGFR-TKI therapy (31.44 [95% CI: 10.28-52.60 months]), compared to EGFR-TKIs only (18.00 [95% CI: 11.31-24.70 months). The corresponding hazard ratio was 0.55 (95% CI: 0.31-0.98, p=0.04). For patients with BMI <24, there was no statistically significant difference between metformin + TKI vs. TKI only (PFS p=0.65, OS p=0.68).

Image: PD

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