FIRST LINE GEFITINIB THERAPY

First-Line Gefitinib for Patients With Advanced Non-Small-Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations Without Indication for Chemotherapy

Inoue A, Kobayashi K, Usui K, et al; North East Japan Gefitinib Study Group
J Clin Oncol. 2009;27:1394-1400. Epub 2009 Feb 17

Summary

Japanese investigators who have been examining the optimal role of the epidermal growth factor receptor (EGFR) inhibitor in patients with non-small-cell lung cancer (NSCLC) conducted a small phase 2 study of gefitinib in patients with NSCLC with poor performance status (PS) and known EGFR mutations. Thirty patients who were considered inappropriate candidates for cytotoxic chemotherapy due to a poor PS -- 22 of whom had PS 3-4 -- were treated with 250 mg/day single-agent gefitinib. The objective response rate was 66%, with a disease control rate of 90%. Further, 79% of patients were reported to have experienced an improvement in their PS. The 1-year survival rate was 63%, with a median overall survival of 17.8 months (range, 12-26 months). There were no reported treatment-associated fatalities.

Viewpoint

This most provocative report suggests that it is reasonable to consider first-line treatment solely with a known inhibitor of EGFR in carefully selected patients with NSCLC and documented EGFR mutations.

Use of the relatively less-toxic targeted therapeutic approach would seem to be a highly rational strategy in this clinical setting. It is important for other investigative groups with similar patient populations to report their experiences in this setting and to confirm (or refute) the impressive observations in this report.

The investigators defined a patient population of which the alternative strategy of employing standard cytotoxic chemotherapy was believed to be inappropriate. Their results provide strong support for future studies that directly compare in a randomized trial single-agent anti-EGFR therapy with standard chemotherapy in the first-line treatment in patients with advanced/metastatic NSCLC and a documented EGFR mutation who would potentially be candidates to receive cytotoxic drugs. Such an approach will be important to document the relative efficacy vs toxicity of these 2 strategies in this difficult clinical setting.