Gefitinib (
Iressa) is an
epidermal growth factor receptor (EGFR)
tyrosine kinase inhibitor that offers treatment for patients with locally advanced or metastatic
non-small cell lung cancer (NSCLC), in particular in those who are harbouring EGFR mutations. In a large phase III trial (IPASS) in
chemotherapy-naive Asian patients with
adenocarcinoma who were never smokers or former light smokers, oral
gefitinib was more effective than
carboplatin plus
paclitaxel in prolonging progression-free survival (PFS). In a prespecified subgroup analysis, EGFR-mutation-positive status was associated with a positive response to
gefitinib treatment. Furthermore, a trial in
chemotherapy-naive patients with NSCLC that was restricted to those with EGFR mutations found that
gefitinib recipients had significantly longer PFS than
carboplatin plus
paclitaxel recipients. In large phase III trials (INTEREST, V-15-32) in unselected, previously treated patients, the overall survival (OS) in
gefitinib recipients was noninferior to, or not significantly different from, that of
docetaxel recipients. In a placebo-controlled trial in previously treated patients (ISEL), pre-planned subgroup analyses in Asian patients and non-smokers showed that in these subgroups
gefitinib prolonged OS, and that EGFR
biomarkers predicted a positive response to
gefitinib.
Gefitinib was also associated with greater improvements in quality of life (QOL) in both
chemotherapy-naive and previously treated patients. A head-to-head trial of
gefitinib versus
erlotinib in EGFR-mutation-positive patients would help position
gefitinib relative to
erlotinib in this population. Further research is also required to identify factors associated with non-response to EGFR-
tyrosine-kinase inhibitors in EGFR-mutation-positive patients.
Gefitinib was a generally well tolerated treatment, with
rash and diarrhoea being the most common treatment-emergent adverse events.
Interstitial lung disease (ILD) is a serious co-morbidity of NSCLC associated with
gefitinib and other
cancer treatments; ILD-type events occurred with an overall incidence of approximately 1% in
gefitinib recipients participating in clinical trials, and were more common in Asian patients. Notably,
gefitinib was associated with significantly fewer haematological and neurological adverse effects than comparator
chemotherapy regimens.
Gefitinib as monotherapy is an effective treatment for patients with locally advanced or metastatic NSCLC with EGFR mutations.