Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR.

Abstract

BACKGROUND:

Non-small-cell lung cancer with sensitive mutations of the epidermal growth factor receptor (EGFR) is highly responsive to EGFR tyrosine kinase inhibitors such as gefitinib, but little is known about how its efficacy and safety profile compares with that of standard chemotherapy.

METHODS:

We randomly assigned 230 patients with metastatic, non-small-cell lung cancer and EGFR mutations who had not previously received chemotherapy to receive gefitinib or carboplatin-paclitaxel. The primary end point was progression-free survival; secondary end points included overall survival, response rate, and toxic effects.

RESULTS:

In the planned interim analysis of data for the first 200 patients, progression-free survival was significantly longer in the gefitinib group than in the standard-chemotherapy group (hazard ratio for death or disease progression with gefitinib, 0.36; P<0.001), resulting in early termination of the study. The gefitinib group had a significantly longer median progression-free survival (10.8 months, vs. 5.4 months in the chemotherapy group; hazard ratio, 0.30; 95% confidence interval, 0.22 to 0.41; P<0.001), as well as a higher response rate (73.7% vs. 30.7%, P<0.001). The median overall survival was 30.5 months in the gefitinib group and 23.6 months in the chemotherapy group (P=0.31). The most common adverse events in the gefitinib group were rash (71.1%) and elevated aminotransferase levels (55.3%), and in the chemotherapy group, neutropenia (77.0%), anemia (64.6%), appetite loss (56.6%), and sensory neuropathy (54.9%). One patient receiving gefitinib died from interstitial lung disease.

CONCLUSIONS:

First-line gefitinib for patients with advanced non-small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival, with acceptable toxicity, as compared with standard chemotherapy. (UMIN-CTR number, C000000376.)

• Authors: Makoto Maemondo, Akira Inoue, Kunihiko Kobayashi, Shunichi Sugawara, Satoshi Oizumi, Hiroshi Isobe, Akihiko Gemma, Masao Harada, Hirohisa Yoshizawa, Ichiro Kinoshita, Yuka Fujita, Shoji Okinaga, Haruto Hirano, Kozo Yoshimori, Toshiyuki Harada, Takashi Ogura, Masahiro Ando, Hitoshi Miyazawa, Tomoaki Tanaka, Yasuo Saijo, Koichi Hagiwara, Satoshi Morita, Toshihiro Nukiwa, North-East Japan Study Group
• Journal: The New England journal of medicine (N Engl J Med) Vol. 362 Issue 25 Pg. 2380-8 (Jun 24 2010) ISSN: 1533-4406 [Electronic] United States
• PMID: 20573926 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: 2010 Massachusetts Medical Society

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• Quinazolines
• Carboplatin
• ErbB Receptors
• Paclitaxel
• Gefitinib

Topics

• Aged
• Antineoplastic Agents (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carboplatin (administration & dosage)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, secondary)
• ErbB Receptors (antagonists & inhibitors, genetics)
• Female
• Gefitinib
• Genes, erbB-1
• Humans
• Lung Neoplasms (drug therapy, genetics, pathology)
• Male
• Middle Aged
• Mutation
• Paclitaxel (administration & dosage)
• Protein Kinase Inhibitors (therapeutic use)
• Quinazolines (therapeutic use)
• Survival Analysis