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Afatinib + dacomitinib is a hypothetical combination of two second-generation, irreversible small molecule tyrosine kinase inhibitors targeting the ErbB family of receptors, including epidermal growth factor receptor (EGFR/ErbB1), HER2/ErbB2, and HER4/ErbB4. Both drugs are approved individually for the treatment of non-small cell lung cancer (NSCLC) with EGFR mutations. Afatinib and dacomitinib covalently bind to their targets, blocking downstream signaling pathways involved in tumor cell proliferation and survival. While both agents have demonstrated efficacy as monotherapies in NSCLC patients with common or uncommon EGFR mutations, there is no clinical evidence supporting their use together as a fixed combination; studies to date have compared them head-to-head rather than in combination[1][2][7]. The rationale for combining these agents would be theoretical synergy through broader or more complete inhibition of the ErbB signaling network.
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