Gefitinib: a review of its use in the treatment of locally advanced/metastatic non-small cell lung cancer.
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.
Sanford
Mark
M
Adis, North Shore, Auckland, New Zealand. demail@adis.co.nz
Scott
Lesley J
LJ
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004347:Drug Interactions; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009362:Neoplasm Metastasis; D011799:Quinazolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib