Indications
Afatinib Dimaleate is used as first-line treatment in EGFR mutation-positive, metastatic non-small cell lung cancer (NSCLC). It is meant for patients whose tumours have non-resistant epidermal growth factor receptor (EGFR) mutations, as detected by an FDA-approved test. The limitation of use is that its safety and efficacy have not been established in patients whose tumours have resistant EGFR mutations. Afatinib Dimaleate is also indicated for previously treated, metastatic squamous NSCLC, that is, for patients whose disease has progressed after platinum-based chemotherapy.
⚠️ Always consult a registered physician before taking any medicine.
Pharmacology
Afatinib binds covalently to the kinase domains of EGFR (ErbB1), HER2 (ErbB2) and HER4 (ErbB4). It blocks tyrosine kinase autophosphorylation irreversibly, and this lowers ErbB signalling. Some mutations in EGFR, including non-resistant mutations in its kinase domain, increase autophosphorylation of the receptor. The receptor then becomes active, sometimes even without a ligand attached, and this can support cell proliferation in NSCLC.
Non-resistant mutations are those in the exons that make up the kinase domain of EGFR, where they lead to increased receptor activation and where efficacy is predicted by 1) clinically meaningful tumor shrinkage with the recommended dose of afatinib and/or 2) inhibition of cellular proliferation or EGFR tyrosine kinase phosphorylation at concentrations of afatinib that can be sustained at the recommended dosage, according to validated methods. The most common of these mutations are exon 21 L858R substitutions and exon 19 deletions.
Afatinib inhibited autophosphorylation and/or in vitro proliferation of cell lines expressing wild type EGFR. It did the same in cell lines expressing selected EGFR exon 19 deletion mutations, exon 21 L858R mutations, or other less common non-resistant mutations, at the afatinib concentrations reached in patients. Afatinib also inhibited in vitro proliferation of cell lines overexpressing HER2.
In nude mice, treatment with afatinib inhibited the growth of implanted tumors that overexpressed either wild type EGFR or HER2, and of tumors in an EGFR L858R/T790M double mutant model.
Pregnancy & Breastfeeding
Afatinib can cause harm to the unborn baby when a pregnant woman takes it. There are no data on the use of Afatinib in pregnant women. There are also no data on whether Afatinib passes into human milk, what it does to a breastfed infant, or whether it affects milk production. Because nursing infants could have serious adverse reactions to Afatinib, a woman who is breastfeeding should be advised not to breastfeed during treatment and for 2 weeks after her final dose.
⚠️ Talk to your doctor before taking any medicine during pregnancy or while breastfeeding.
Dosage Reference
⚠️ Reference ranges from official sources only. Consult your doctor for personalized dosing.
Side Effects & Interactions
Side Effects
No side-effect data recorded yet.