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Lung Cancer

Gefitinib in Advanced Non-Small Cell Lung Cancer: Does It Deserve a Second Chance?

Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, USA

Key Words. Epidermal growth factor receptor • EGFR • Tyrosine kinase inhibitor • TKI • Erlotinib • Non-small cell lung cancer • NSCLC • Second-line therapy

Correspondence: Thomas E. Stinchcombe, M.D., Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, 3009 Old Clinic Building, Cb 7305, Chapel Hill, North Carolina 27599-7305, USA. Telephone: 919-966-9268; Fax: 919-966-6735; e-mail: Thomas_Stinchcombe{at}med.unc.edu

Received January 25, 2008; accepted for publication April 6, 2008; first published online in THE ONCOLOGIST Express on September 10, 2008.

Disclosure: Employment/leadership position: None; Intellectual property rights/inventor/patent holder: None; Consultant/advisory role: None; Honoraria: None; Research funding: Mark A. Socinski, AstraZeneca. Genentech; Ownership interest: None; Expert testimony: None; Other: Speakers' bureau: Thomas E. Stinchcombe, Genentech; Speakers' bureau: Mark A. Socinski. Genentech. The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors, planners, independent peer reviewers, or staff managers.

There has been intense investigation into the epidermal growth factor receptor (EGFR) as a therapeutic target in the treatment of non-small cell lung cancer (NSCLC). Currently there are two EGFR tyrosine kinase inhibitors, erlotinib and gefitinib, approved for the treatment of advanced NSCLC. In a phase III trial (BR.21), treatment with erlotinib resulted in a statistically significant improvement in overall survival in patients who had experienced progression after one or two previous chemotherapy treatments in comparison with best supportive care (BSC). In contrast, in the Iressa Survival Evaluation in Lung Cancer (ISEL) trial, treatment with gefitinib did not result in a statistically significant improvement in overall survival time in comparison with BSC in patients who had received one or two previous chemotherapy treatments and were refractory to or intolerant of the previous chemotherapy. After the results of the ISEL trial, the U.S. Food and Drug Administration restricted the use of gefitinib, and gefitinib was effectively removed from routine clinical practice within the U.S. However, gefitinib was approved in other countries and clinical trials investigating gefitinib continued. Recently the Iressa Non-small cell lung cancer Trial Evaluating REsponse and Survival against Taxotere (INTEREST) trial met the primary endpoint of demonstrating noninferiority in terms of overall survival for gefitinib (250 mg daily) in comparison with docetaxel (75 mg/m² every 3 weeks). Patients treated with gefitinib experienced a lower rate of treatment-related toxicity and higher rate of improvement in quality of life. Results of recent gefitinib trials have been provocative, and suggest a role for gefitinib in the treatment of advanced NSCLC.