Iressa® Produces Survival Advantage in Selected Patients with Refractory NSCLC
Updated results of the phase III Iressa®Survival Evaluation in Lung Cancer (ISEL) indicate that Iressa (gefitinib) produces a survival advantage in patients with Asian ethnicity andthose who have never smoked, but still does not show an improvement in survival for the overall group.These findings were presented at the Presidential Symposium of the 11th World Conference on Lung Cancer held in Barcelona, Spain, July 3-6, 2005.
Lung cancer is the leading cause of cancer-related deaths in the United States and Europe. The most common type of lung cancer, NSCLC, is a malignancy that arises from the tissues of the lung. Under most circumstances, NSCLC is not curable unless the disease is treated surgically before it has spread. Current treatments attempt to destroy cancer cells or prevent further tumor growth. They include surgery, chemotherapy and radiation. One approach to treating NSCLC is a drug known as Iressa, which stops the cancerous cell growth by targeting the lung cancer cell specifically. Iressa is an orally administered selective inhibitor of epidermal growth factor receptor-tyrosine kinase. Epidermal growth factor receptor is expressed, over-expressed or dysregulated in many human solid tumors, including NSCLC. Activation of this receptor is believed to promote tumor growth by blocking programmed cell death and by increasing cell proliferation, adhesion and invasive capacity and motility.
These activities have resulted in the targeting of the epidermal growth factor receptor for therapeutic purposes. Treatment with Iressa results in response rates of 11 percentto 18 percentin patients with advanced NSCLC who have failed prior chemotherapy. Combining chemotherapy with Iressa does not improve the response rate or survival over Iressa alone. A retrospective study of 23,480 patients with NSCLC receiving Iressa on a compassionate basis showed a one-year survival of 33 percent. Early observations suggested that women with adencarcinoma had the highest response to Iressa. Other factors associated with response to Iressa include never smoking and bronchioloalveolar cell type. Somatic mutations have also been identified in the tyrosine kinase domain of the EGFR gene in Iressa-responsive lung cancer. These data suggest that only a small fraction of patients with NSCLC will benefit from Iressa using objective response criteria.
There were 1692 patients from 210 centers in 28 countries involved in the currentstudy. Patients had locally advanced or metastatic NSCLC. They had received one or two prior chemotherapy regimens and were intolerant or refractory to their most recent treatment regimen, as defined by progressive disease within 90 days of their last dose of chemotherapy. Patients were randomly assigned to receive Iressa plus best supportive care (BSC) or placebo plus BSC.
Results indicate that, overall, Iressa did not produce a survival advantage.However, a statistically significant survival advantage was reported for patients with Asian ethnicity and never smokers.Patientswith adenocarcinoma did not experience a survival advantage (Table 1).
Table 1: Iressa in the Treatment of Refractory Advanced NSCLC
The response rate was higher among never smokers (18percent) than ever smokers (5percent).However, patients with Asian ethnicity did not appear to derive a benefit in response compared to patients treated with placebo (12percentversus6.5percent).
Adverse events that occurred at higher frequency among patients receiving Iressa include rash (37percentversus10percentfor patients receiving placebo) and diarrhea (27percentversus9percentfor patients receiving placebo.) There was no difference in serious adverse events for patients who received Iressa (19percent) and placebo (17percent). Patients with NSCLC who have characteristics of responding patients,such as Asian ethnicity, never smokers, adenocarcinoma or bronchioalveolar cell types,may wish to discuss possible treatment with Iressa with their physician.
Reference: Thatcher N, Chang A, Parikh P, et al. ISEL: a phase III survival study comparing gefitinib (IRESSA) plus best supportive care (BSC) with placebo plus BSC in patients with advanced non-small cell lung cancer (NSCLC) who had received one or two prior chemotherapy regimens. Proceedings from the 11th World Conference on Lung Cancer, Barcelona, Spain. 2005; Abstract #Pr4.
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