Gefitinib: a review of its use in adults with advanced non-small cell lung cancer
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Gefitinib (Iressa®) is a selective small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR TKI) indicated for the treatment of adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating mutations of EGFR tyrosine kinase. Large phase III or IV clinical trials in patients with locally advanced or metastatic NSCLC showed that gefitinib as first- or subsequent-line treatment significantly prolonged progression-free survival (PFS) and improved objective response rates and/or health-related quality of life parameters in patients with activating EGFR mutations and in clinically selected patients (e.g., Asian patients or never-smokers) who are more likely to harbour these mutations. Overall survival did not increase significantly with gefitinib, although post-study treatments may have had a confounding effect on this outcome. Gefitinib was generally well tolerated in these studies, with mild or moderate skin reactions, gastrointestinal disturbances and elevations in liver enzymes among the most common adverse reactions in gefitinib recipients; interstitial lung disease has also been reported in <6 % of gefitinib recipients. Compared with chemotherapy, gefitinib as first- or subsequent-line therapy provided similar or greater PFS benefit and was generally associated with fewer haematological adverse events, neurotoxicity, asthenic disorders, as well as grade ≥3 adverse events. Although the position of gefitinib with respect to other EGFR TKIs is not definitively established, current evidence indicates that gefitinib monotherapy is an effective and generally well-tolerated first- or subsequent-line treatment option for patients with NSCLC and activating EGFR mutations who have not received an EGFR TKI previously.
KeywordsGefitinib Epidermal growth factor receptor tyrosine kinase inhibitor Non-small cell lung cancer
Data selection sources
Relevant medical literature (including published and unpublished data) on gefitinib was identified by searching databases including MEDLINE (from 1946) and EMBASE (from 1996) [searches last updated 16 January 2015], bibliographies from published literature, clinical trial registries/databases and websites. Additional information was also requested from the company developing the drug.
Gefitinib, non-small cell lung cancer, NSCLC, EGFR-mutation positive, locally advanced, metastatic, first-line, second-line.
Studies in patients with locally advanced or metastatic non-small cell lung cancer who received gefitinib as first-line or subsequent-line therapy. When available, large, well-designed, comparative trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit. Sohita Dhillon is a salaried employee of Adis/Springer.
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