ROCKVILLE, Maryland—The Food and Drug Administration (FDA) has granted accelerated approval to Iressa tablets (gefitinib, AstraZeneca) as monotherapy for the treatment of advanced non-small-cell lung cancer (NSCLC) in patients whose disease has progressed despite treatment with platinum-based and docetaxel(Drug information on docetaxel) (Taxotere) chemotherapy.
The Oncologic Drugs Advisory Committee (ODAC) had recommended approval of Iressa on September 24, 2002. However, the FDA delayed action on the recommendation for 3 months to analyze new Japanese data that indicated Iressa was associated with an unexpected and often-fatal rate of interstitial lung disease (ILD).
As a condition of approval, Astra-Zeneca agreed to conduct three phase IV postmarketing trials of Iressa ( see box ). Accelerated approval is granted to drugs that have shown indications of benefit in serious or life-threatening diseases over available therapies or, as in the case of Iressa, in conditions for which no effective treatment exists.
"An essential part of our accelerated approval process is the further study of the new treatment after it is on the market," said FDA commissioner Mark B. McClellan, MD, PhD. "In the case of Iressa, studies are needed to confirm clinical benefit, understand better which patients benefit, and evaluate long-term safety."
Although the drug’s mechanism of action is not fully understood, Iressa was designed to inhibit growth stimulatory signals by blocking several tyrosine kinases, including one associated with the epidermal growth factor receptor. This blocking results in an inhibition of cancer cell proliferation and an increase in apoptosis. The drug is administered as a 250-mg tablet taken once a day.
Phase II Trial
The FDA approved Iressa on the basis of findings from a phase II trial that studied two doses of the drug in 216 patients who had previously failed platinum-based and docetaxel chemotherapy. In reviewing the data, ODAC concluded that the 10% Iressa response rate in these patients was reasonably likely to predict clinical benefit, but told the FDA that symptom improvement could not be adequately evaluated without a randomized, blinded study.
