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The Food and Drug Administration has approved Iressa (gefitinib) as a monotherapy for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors harbor specific types of epidermal growth factor receptor (EGFR) gene mutations, as detected by an FDA-approved test.

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Iressa, marketed by AstraZeneca, originally received accelerated approval in 2003 for the treatment of patients with advanced NSCLC after disease progression on platinum doublet chemotherapy and docetaxel. However, Iressa was voluntarily withdrawn from the market after subsequent confirmatory trials failed to verify clinical benefit. This current approval is for a different patient population (EGFR mutation-positive, previously untreated) than the 2003 approval was for.


Iressa is an oral inhibitor that blocks proteins that promote the development of cancerous cells with certain EGFR mutations, including exon 19 deletions or exon 21 L858R substitution gene mutations, the most common EGFR mutations in NSCLC.


The FDA also approved the therascreen EGFR RGQ PCR Kit as a companion diagnostic test to identify patients with tumors having the EGFR gene mutations in order to determine which patients would be appropriate for Iressa.


The kit provides reagents optimized for rapid and sensitive detection of 21 somatic mutations using the QIAamp DNA FFPE Tissue Kit and the Rotor-Gene Q MDX.


The diagnostic test is made by QIAGEN Manchester Ltd., which is based in the United Kingdom.


"Iressa offers another effective first-line therapy option for selected lung cancer patients. This approval provides further support for a highly targeted approach to treating cancer," Richard Pazdur, MD, Director of the FDA's Office of Hematology and Oncology Products in the Center for Drug Evaluation and Research, said in a news release.


The agency also granted Orphan Drug designation to Iressa for the treatment of patients with EGFR mutation-positive metastatic NSCLC. The Orphan Drug designation-to encourage development of drugs in the diagnosis, prevention, or treatment of a medical condition affecting fewer than 200,000 people in the U.S.-grants a product market exclusivity for a seven-year period if the sponsor complies with certain FDA specifications, as well as tax credits and prescription drug user fee waivers. The designation does not, though, shorten the duration of the regulatory review and approval process.


Safety and efficacy for Iressa were evaluated in a multi-center, single-arm clinical trial of 106 patients with previously untreated, EGFR mutation-positive metastatic NSCLC. Approximately half of patients had their tumors shrink after treatment with Iressa, with the response lasting an average of six months. Response rates were similar for patients whether their tumors had EGFR exon 19 deletions or exon 21 L858R substitution mutations.


Another study supporting those results for Iressa found that of a subgroup of 186 patients with EGFR mutation-positive metastatic NSCLC who were randomized to receive either Iressa or carboplatin/paclitaxel as first-line treatment, the patients receiving Iressa had longer progression-free survival (10.9 months) compared with the patients receiving the combination therapy (7.4 months), according to a news release from the drug company.


Sixty-seven percent of the patients treated with Iressa responded, with a median duratin of response of 9.6 months, compared with 41 percent of patients responding to the combination therapy, with a median response duration of 5.5 months.


Serious side effects for Iressa included interstitial lung disease, liver damage, gastrointestinal perforation, severe diarrhea, and ocular disorders. The most common side effects of Iressa are diarrhea and skin reactions (including rash, acne, dry skin, and pruritus).

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