Gefitinib (Iressa) Back in the US for Lung Cancer, Now as First-Line

Nick Mulcahy

July 13, 2015

The US Food and Drug Administration today announced the approval of gefitinib (Iressa, AstraZeneca) for the first-line treatment of patients with metastatic non–small cell lung cancer (NSCLC) whose tumors contain specific types of epidermal growth factor receptor (EGFR) gene mutations.

A companion test was also approved to identify appropriate patients.

Although NSCLC is the most common type of lung cancer, EGFR gene mutations occur in only about 10% of NSCLC tumors, according to the National Cancer Institute.

A kinase inhibitor, gefitinib is intended for the treatment of patients whose tumors express the most common types of EGFR mutations in NSCLC tumors: exon 19 deletions or exon 21 L858R substitution gene mutations.

The companion diagnostic test, known as the therascreen EGFR RGQ PCR Kit, identifies patients who have these very specific EGFR gene mutations.

"Gefitinib 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," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, in a press statement.

The approval of gefitinib is based on results from a multicenter, single-group clinical trial of 106 patients with metastatic NSCLC that was EGFR mutation–positive and previously untreated.

After treatment with gefitinib (250 mg once daily), roughly 50% of patients had an objective response, which was the study's primary endpoint. The average length of response was 6 months.

The response rates were similar in patients whether their tumors had EGFR exon 19 deletions or exon 21 L858R substitution mutations.

These results are bolstered by a retrospective analysis of another clinical trial, in which a subgroup of 186 patients had metastatic, EGFR-positive NSCLC and received first-line treatment with gefitinib. The patients randomly assigned to receive gefitinib had better progression-free survival than patients receiving standard chemotherapy (up to six cycles of carboplatin/paclitaxel).

Gefitinib may cause serious adverse effects including interstitial lung disease, liver damage, gastrointestinal perforation, severe diarrhea, and ocular disorders, according to the FDA. The most common adverse effects are diarrhea and skin reactions (including rash, acne, dry skin, and pruritus).

The new approval represents a reversal of fortune for the drug in the United States, which has had an unusual history.

Gefitinib originally received accelerated approval in 2003 for the treatment of patients with advanced NSCLC after progression on platinum doublet chemotherapy and docetaxel. However, the drug was withdrawn from the market after confirmatory trials failed to verify clinical benefit; at the time, it was not known that the drug effectiveness was limited to mutation-specific patients.

Thus, the current approval is for a different patient population (EGFR mutation–positive, previously untreated) than the 2003 approval.

The United States now joins more than 60 countries worldwide in approving the drug for these EGFR-positive patients.

The FDA granted gefitinib an orphan drug designation for this indication.

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