A pooled analysis of two phase II trials evaluating metformin plus platinum-based chemotherapy in advanced non-small cell lung cancer
Abstract
BACKGROUND: Despite a wealth of preclinical and observational data, prospective data regarding the use of metformin in lung cancer is extremely limited.
METHODS: We pooled individualized data from two prospective trials evaluating metformin plus platinum-based chemotherapy, with or without bevacizumab, in non-diabetic patients with untreated advanced NSCLC. In addition to reporting on clinical efficacy and safety endpoints, we also explored metformin's activity in key molecular cohorts.
RESULTS: 33 patients were included in the pooled analysis, of whom 70% were current or previous smokers. 82% had standard tissue molecular testing results available. KRAS, EGFR, and LKB1 mutation prevalence was 48%, 26%, and 8.3%, respectively. Composite median PFS was 6 months for all patients (95% CI: [1.36, 7.96]), 7.2 months for KRAS mutants (95% CI: [1.18, 9.21]), and 6.6 months for EGFR mutants (95% CI: [1.18, 15.29]). Composite median OS was 14.8 months for all patients (95% CI: [8.25, 19.99]), 17.5 months for KRAS mutants (95% CI: [8.86, 26.96]), and 13.3 months for EGFR mutants (95% CI: [2.60, 25.86]). Lymphopenia was the most common grade 3 AE (12%), followed by leukopenia, nausea, vomiting, and hypertension (9% each). There were 2 grade 4 AEs, neutropenia (21%) and sepsis (3%), and 1 grade 5 AE (colonic perforation) attributed to bevacizumab.
CONCLUSION: Our results confirm the previously shown efficacy and tolerability of metformin in combination with chemotherapy and highlight…
How strong is the evidence?
Evidence Hub reads this as a secondary / pooled analysis, 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: 33 participants or records.
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