erlotinib + gefitinib + icotinib + metformin

A combination therapy consisting of EGFR tyrosine kinase inhibitors (erlotinib, gefitinib, and icotinib) and metformin. This combination has shown synergistic effects in treating non-small cell lung cancer (NSCLC), particularly in cases with EGFR mutations and EGFR-TKI resistance. Metformin enhances the efficacy of EGFR-TKIs by targeting alternative pathways, particularly the IGF-1R pathway, which is often implicated in EGFR-TKI resistance. Studies have demonstrated that this combination can overcome primary resistance to EGFR-TKIs, induce apoptosis in resistant cancer cells, and improve progression-free survival and overall survival in NSCLC patients.