On May 5, 2003,
gefitinib (
Iressa),
ZD1839) 250-mg
tablets received accelerated approval by the U.S. Food and Drug Administration as monotherapy treatment for patients with locally advanced or metastatic
non-small cell lung cancer (NSCLC) after failure of both
platinum-based and
docetaxel chemotherapies. Information provided in this summary includes efficacy and safety results of relevant clinical trials. Effectiveness was demonstrated in a randomized, double-blind, phase II, multicenter trial comparing two oral doses of
gefitinib (250 mg/day versus 500 mg/day). Two hundred sixteen patients were enrolled. The 142 patients who were refractory to or intolerant of a
platinum and
docetaxel comprised the evaluable population for the efficacy analysis. A partial
tumor response occurred in 14% (9 of 66) of patients receiving
gefitinib 250 mg/day and in 8% (6 of 76) of patients receiving
gefitinib 500 mg/day. The overall objective response rate for both doses combined was 10.6% (15 of 142 patients) (95% confidence interval 6.0%-16.8%). Responses were more frequent in females and in nonsmokers. The median duration of response was 7.0 months (range 4.6-18.6+ months). Other submitted data included the results of two large trials conducted in
chemotherapy-naive, stage III and IV NSCLC patients. Patients were randomized to receive
gefitinib (250 mg or 500 mg daily) or placebo, in combination with either
gemcitabine plus
cisplatin (n = 1,093) or
carboplatin plus
paclitaxel (n = 1,037). Results from those studies showed no benefit (response rate, time to progression, or survival) from adding
gefitinib to
chemotherapy. Consequently, gefinitib is only recommended for use as monotherapy. Common adverse events associated with
gefitinib treatment included
diarrhea,
rash,
acne, dry skin,
nausea, and
vomiting. Most toxicities were Common Toxicity Criteria grade 1 or 2.
Interstitial lung disease (ILD) has been observed in patients receiving
gefitinib. Worldwide, the incidence of ILD is about 1% (2% in the Japanese postmarketing experience and about 0.3% in a U.S. expanded access program). Approximately one-third of the cases were fatal. Physicians should promptly evaluate new or worsening pulmonary symptoms. If ILD is confirmed, appropriate management includes discontinuation of
gefitinib.
Gefitinib was approved under accelerated approval regulations on the basis of a
surrogate end point response rate. No controlled
gefitinib trials, to date, demonstrate a clinical benefit, such as improvement in disease-related symptoms or greater survival. Accelerated approval regulations require the sponsor to conduct further studies to verify that
gefitinib therapy produces such a benefit.