Approval of Targeted Lung Cancer Drug Iressa Culminates Long Research Trail

The Food and Drug Administration’s approval of the drug Iressa® for a form of metastatic lung cancer represents a return to prominence for the compound that launched the era of targeted therapy in lung cancer – even if that wasn’t clear at the time of its original clinical trial in patients.

The FDA approved Iressa (gefitinib) as a first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) whose tumor cells harbor specific mutations in the gene EGFR.

“The approval of Iressa is important because newly diagnosed patients with EGFR-mutant lung cancer now have more treatment options,” said Pasi A. Jänne, MD, PhD, director of the Lowe Center for Thoracic Oncology at Dana-Farber. “Newly diagnosed patients with lung cancer should ask their doctors about getting tested for an EGFR mutation to see if they may be candidates to be treated with Iressa.”

Iressa becomes the third targeted therapy – after Tarceva® (erlotinib) and Gilotrif® (afatinib) – to gain approval specifically for EGFR-mutant disease, but it actually led the way for the others.

It originally received accelerated approval in 2003 for the treatment of patients with advanced NSCLC whose disease continued to advance after treatment with standard chemotherapy. It was voluntarily withdrawn from the market when later clinical trials failed to show that it offered patients any clinical benefit.

When a team of researchers at Dana-Farber and a separate group at Massachusetts General Hospital began delving more deeply into the trial data, they noticed something intriguing: While the vast majority of patients indeed did not benefit from Iressa, a small number of patients had spectacular results – full remissions that lasted a year or more in some cases.

By piecing together evidence from laboratory and clinical studies, researchers deduced that Iressa works only in patients where mutations cause too much EGFR protein to be produced, rather than in all patients with NSCLC.

This week’s approval of Iressa is based on a clinical trial that tested the drug as front-line therapy in 106 patients who had previously untreated, metastatic NSCLC that was positive for EGFR mutations. The results showed that tumors shrank in about 50 percent of patients after treatment and this effect lasted an average of six months.

FDA approval authorizes the use of Iressa in NSCLC patients whose tumor cells carry the most common types of EGFR mutations, meaning the drug could potentially be used in thousands of patients around the world. According to the American Cancer Society, nearly 190,000 people are diagnosed annually in the U.S. with NSCLC, about 10 percent of whom carry EGFR mutations in their tumor cells.

The choice of whether to treat patients with Iressa, Tarceva, or afatinib depends on a variety of factors, including the drugs’ side effects, which can be severe, Jänne said. A head-to-head comparison of Iressa and afatinib is currently underway.