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FDA Approves Gefitinib (Iressa) for First-Line Treatment of Lung Cancer Patients

Companion test also approved to identify appropriate patients

The FDA has approved gefitinib (Iressa, AstraZeneca Pharmaceuticals) 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.

Lung cancer is the leading cause of cancer-related death among men and women in the U.S. and, although more common in men, the number of deaths from lung cancer in women is increasing. According to the National Cancer Institute, an estimated 221,200 Americans will be diagnosed with lung cancer and 158,040 will die from the disease in 2015. NSCLC is the most common type of lung cancer. Mutations in the EGFR gene are present in approximately 10% of NSCLC tumors.

Gefitinib is a kinase inhibitor that blocks proteins that promote the development of cancerous cells with certain EGFR mutations. The drug is intended for the treatment of patients whose tumors express the most common types of EGFR mutations in NSCLC (exon 19 deletions or exon 21 L858R substitution gene mutations). The therascreen EGFR RGQ PCR Kit (Qiagen Manchester Ltd) was approved as a companion diagnostic test to identify patients with tumors with the EGFR gene mutations to determine which patients would be appropriate for treatment with gefitinib.

The FDA granted gefitinib an “orphan drug” designation for the treatment of EGFR mutation-positive metastatic NSCLC. This designation is given to drugs that are intended to treat rare diseases and provides financial incentives to promote their development.

The efficacy and safety of gefitinib was demonstrated in a single-arm clinical trial of 106 patients with previously untreated, EGFR mutation-positive, metastatic NSCLC. The study’s primary endpoint was the objective response rate. The patients received gefitinib 250 mg once daily. The results showed that tumors shrank in approximately 50% of the patients after treatment, and that this effect lasted an average of 6 months. The response rates were similar regardless of whether patients’ tumors had EGFR exon 19 deletions or exon 21 L858R substitution mutations.

These results were supported by a retrospective analysis of another clinical trial, which identified a subgroup of 186 patients with EGFR mutation-positive metastatic NSCLC who were receiving first-line treatment. These patients were randomly assigned to receive gefitinib or up to six cycles of carboplatin/paclitaxel. The results from this subgroup analysis suggested an improvement in progression-free survival with gefitinib compared with carboplatin/paclitaxel.

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

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

Source: FDA; July 14, 2015.

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