anlotinib + afatinib

Anlotinib + afatinib is a combination therapy consisting of two oral small molecule tyrosine kinase inhibitors (TKIs) used in the treatment of non-small cell lung cancer (NSCLC), particularly in patients with resistance to prior EGFR-TKI therapies. Anlotinib is a multi-target TKI that inhibits vascular endothelial growth factor receptors (VEGFR 2/3), fibroblast growth factor receptors (FGFR 1–4), platelet-derived growth factor receptor alpha and beta, c-Kit, and RET, thereby blocking tumor angiogenesis and proliferative signaling. Afatinib is an irreversible inhibitor of the ErbB family of receptors, including epidermal growth factor receptor (EGFR/ErbB1), HER2/ErbB2, and ErbB4. The rationale for combining these agents lies in their complementary mechanisms—afatinib targets EGFR-driven tumor proliferation while anlotinib suppresses angiogenesis and additional proliferative pathways—potentially overcoming resistance to single-agent EGFR-TKIs. This combination has shown partial responses in case reports for NSCLC patients who have progressed on previous lines of therapy[7][4]. Clinical data are limited but suggest potential benefit in select populations.