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Clinical Trial Results

Summaries of Newsworthy Clinical Trial Results
  • Posted: 08/12/2010

Gefitinib Improves Progression-free Survival for Metastatic Lung Cancers with EGFR Mutations

Adapted from the NCI Cancer Bulletin.

Patients newly diagnosed with metastatic non-small cell lung cancer (NSCLC) who received gefitinib (Iressa) had significantly higher response rates and longer progression-free survival compared with patients who received carboplatin plus paclitaxel (73.7 percent versus 30.7 percent and 10.8 months versus 5.4 months, respectively), according to results of a phase III trial conducted in Japan. The results were published in the June 24, 2010, New England Journal of Medicine.

All patients enrolled in the study had mutant versions of the epidermal growth factor receptor (EGFR) that were sensitive to the tyrosine kinase inhibitor (TKI) gefitinib. The patients did not have the EGFR T790M mutation, which confers resistance to TKIs, and they had not been previously treated with chemotherapy.

The researchers, led by Makoto Maemondo, M.D., Ph.D., of the Miyagi Cancer Center in Miyagi, Japan, believe that this study establishes the clinical benefit of an EGFR tyrosine kinase inhibitor as first-line therapy in patients with NSCLC and sensitive EGFR mutations.“If gefitinib is administered as second-line or third-line treatment,” he and his colleagues wrote, “patients may miss the opportunity to receive treatment because of rapidly progressive disease during or after first-line treatment.”

The trial was stopped early in 2009 after a planned interim analysis of the first 200 patients revealed a 70 percent reduction in disease progression or death in patients receiving gefitinib. Ultimately, 230 patients from 43 institutions in Japan were enrolled and analyzed. At 1 year, 42.1 percent of patients receiving gefitinib had not progressed, compared with 3.2 percent of those receiving chemotherapy; after 2 years, all chemotherapy patients had progressed, while 8.4 percent of those receiving gefitinib still had not. Women had longer progression-free survival than men.

Patients who completed their first-line therapy or whose disease progressed while receiving chemotherapy were allowed to cross over and receive gefitinib, and 106 out of 112 did so. Fifty-nine percent of these patients responded to second-line therapy with gefitinib. This crossover, the researchers wrote, may have affected the overall survival difference between the two study arms, which was not statistically significant.

Gefitinib fell out of favor in the United States after a 2005 clinical trial indicated the drug had little benefit in unselected patients, and the drug currently has a  restricted label in this country, where erlotinib (Tarceva) is the approved second-line EGFR TKI of choice. Both gefitinib and erlotinib work in a similar way, and patients with sensitive EGFR mutations are also very responsive to erlotinib treatment.

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