Afatinib* is an irreversible ErbB Family Blocker that is an oral, once daily investigational targeted therapy.1
The ErbB Family of receptors consists of four related members: EGFR (ErbB1), HER2 (ErbB2), ErbB3, and ErbB4.2 These receptors are often overexpressed or mutated in many cancers, including lung, breast, head and neck, and colorectal cancers. An active ErbB-receptor is formed by the union of two molecules, a process called dimerisation. Dimers can be formed between identical receptors e.g. EGFR+EGFR (homodimers) or different receptors e.g. EGFR+HER2 (heterodimers). The ErbB Family of receptors are involved in fundamental cellular processes including cell proliferation, migration, metabolism and survival3, which allow the tumour cells to grow and proliferate.
Inhibiting the ErbB receptor signalling may play a critical role in the prevention of tumour growth and spread. Afatinib* irreversibly binds to the intracellular tyrosine kinase domain of ErbB Family receptors and inhibits the downstream signalling cascade, which in turn may inhibit cell growth and induce apoptosis (programmed cell death) in cancer cells.
Afatinib* is currently being investigated for various tumour types. Afatinib* is in Phase III clinical development in NSCLC, breast cancer and head and neck cancer.2,4
The irreversible binding of afatinib* is unlike other compounds which are reversible in that it provides a sustained, selective, covalent and complete ErbB Family Blockade. This means that afatinib* may provide the potential benefits of improved inhibition of tumour cell proliferation and efficacy across a broad range of cancers compared to EGFR Tyrosine Kinase Inhibitors (TKIs), which offer single, reversible, receptor blocking.5
*Afatinib is an investigational compound.
Its safety and efficacy have not yet been fully established