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Gefitinib for Advanced Non–Small-Cell Lung Cancer

Patients with EGFR mutations and poor performance status benefited from first-line therapy.

Systemic platinum-based doublet chemotherapy improves survival in non–small-cell lung cancer (NSCLC) patients who have good performance status (PS). However, those with poor PS are generally unable to tolerate cytotoxic therapy. Consequently, these patients usually are given best supportive care (BSC), and most die within 4 months. Japanese investigators recently showed that a small group of patients with mutations of the epidermal growth factor receptor (EGFR) gene achieved high overall response rates (ORR, 75%) and long median progression-free survival (PFS, 9.7 months) when administered gefitinib (Iressa), an EGFR tyrosine kinase inhibitor (TKI) with less toxicity than cytotoxic agents (J Clin Oncol 2006; 24:3340).

To further evaluate the efficacy of gefitinib, the same investigators have conducted a prospective, multicenter, phase II study involving 30 chemotherapy-naive NSCLC patients with poor PS (including 22 with PS of 3–4). All patients carried EGFR mutations (determined by testing cytologic specimens with a peptide nucleic acid–locked nucleic acid polymerase chain reaction technique). Specimens were obtained mainly from sputum samples, bronchial washings, pleural effusions, and needle aspirations. Patients received gefitinib (250 mg daily) until they experienced disease progression or intolerable toxicity.

At median follow-up of 17.8 months, ORR was 66%, median PFS was 6.5 months, median survival time (MST) was 17.8 months, and 1-year overall survival was 63%. Performance status improved in 79% of patients (P<0.00005), 68% of whom improved from PS 3 to PS 1. Five patients who received post-gefitinib therapy after disease progression achieved longer MSTs than the remaining patients who received BSC after progression (11.7 months and 8.2 months; P=0.122). Preregistered patients without EGFR mutations achieved MSTs of 3.5 months.

Comment: These investigators have defined a subpopulation of patients who benefit from gefitinib therapy. As an editorialist notes, various testing methods — including EGFR mutation analysis, immunohistochemistry, fluorescence in situ hybridization (FISH), and proteomics — could be used to identify patients who are likely to benefit from EGFR-TKI therapy. Although the optimal test has yet to emerge, the ability to use cytologic specimens is promising, considering that many patients are unable to undergo invasive sampling of larger tumor specimens. As molecular medicine evolves, clinicians will have better tools to identify patients likely to benefit from specific therapies; in the process, individual patient survival and quality of life should improve.

— Lin-Chi Chen, MD, PhD

Dr. Chen is a medical oncologist specializing in lung cancer at the Nevada Cancer Institute.

Published in Journal Watch Oncology and Hematology April 28, 2009

Citation(s):

Inoue A et al. First-line gefitinib for patients with advanced non–small-cell lung cancer harboring epidermal growth factor receptor mutations without indication for chemotherapy. J Clin Oncol 2009 Mar 20; 27:1394.

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• Medline abstract (Free)

Langer CJ. The "Lazarus Response" in treatment-naïve, poor performance status patients with non–small- cell lung cancer and epidermal growth factor receptor mutation. J Clin Oncol 2009 Mar 20; 27:1350.

• Original article (Subscription may be required)
• Medline abstract (Free)