Afatinib (Gilotrif™, Giotrif(®)) is an orally administered, irreversible inhibitor of the ErbB family of
tyrosine kinases.
Afatinib downregulates ErbB signalling by covalently binding to the
kinase domains of
epidermal growth factor receptor (EGFR), human
epidermal growth factor receptor (HER) 2 and HER4, resulting in irreversible inhibition of
tyrosine kinase autophosphorylation; it also inhibits transphosphorylation of HER3.
Afatinib is approved as monotherapy for the treatment of EGFR
tyrosine kinase inhibitor (TKI)-naïve adults with locally advanced or metastatic
non-small cell lung cancer (NSCLC) with activating EGFR mutations in the EU, and for the first-line treatment of patients with metastatic NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by a US FDA-approved test in the US. In two randomized, open-label, multinational phase III trials, progression-free survival was significantly prolonged with
afatinib compared with
pemetrexed plus
cisplatin (LUX-Lung 3) or
gemcitabine plus
cisplatin (LUX-Lung 6) in treatment-naïve patients with advanced NSCLC with activating EGFR mutations. The objective response rate was significantly higher with
afatinib than with
pemetrexed plus
cisplatin or
gemcitabine plus
cisplatin, and patient-reported outcomes for symptoms such as
cough and dyspnoea and certain health-related quality of life measures significantly favoured
afatinib versus
pemetrexed plus
cisplatin or
gemcitabine plus
cisplatin.
Afatinib also showed efficacy in EGFR TKI-naïve patients with advanced
lung adenocarcinoma and activating EGFR mutations who had received no more than one prior
chemotherapy regimen for advanced disease, according to the results of the noncomparative, multinational, phase II LUX-Lung 2 trial. Oral
afatinib had a manageable tolerability profile. EGFR-mediated adverse events (e.g. diarrhoea,
rash/
acne) were generally managed using
dose reduction and delays. In conclusion,
afatinib is a valuable new option for use in treatment-naïve or EGFR TKI-naïve patients with advanced
lung adenocarcinoma and activating EGFR mutations.