Relative abundance of EGFR mutations predicts benefit from gefitinib treatment for advanced non-small-cell lung cancer.

Abstract

PURPOSE:

Our aim was to determine whether abundance of epidermal growth factor receptor (EGFR) mutations in tumors predicts benefit from treatment with EGFR-tyrosine kinase inhibitors (TKIs) for advanced non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS:

We detected EGFR mutations in 100 lung cancer samples using direct DNA sequencing and amplification refractory mutation system (ARMS). Mutation-positive tumors by both methods carried high abundance of EGFR mutations. Tumors that were mutation positive by ARMS but mutation negative by direct DNA sequencing harbored low abundance of EGFR mutations. Mutation-negative tumors by both methods carried wild-type EGFR. All patients received gefitinib treatment. The correlation between EGFR mutation abundance and clinical benefit from gefitinib treatment was analyzed.

RESULTS:

Of 100 samples, 51 and 18 harbored high and low abundances of EGFR mutations, respectively; 31 carried wild-type EGFR. Median progression-free survival (PFS) was 11.3 (95% CI, 7.4 to 15.2) and 6.9 months (95% CI, 5.5 to 8.4) in patients with high and low abundances of EGFR mutations, respectively (P = .014). Median PFS of patients with low abundance of EGFR mutations was significantly longer than that of those with wild-type tumors (2.1 months; 95% CI, 1.0 to 3.2; P = .010). Objective response rates (ORRs) were 62.7%, 44.4%, and 16.1%, and overall survival (OS) rates were 15.9 (95% CI, 13.4 to 18.3), 10.9 (95% CI, 2.7 to 19.1), and 8.7 months (95% CI, 4.6 to 12.7) for patients with high abundance of EGFR mutations, low abundance of EGFR mutations, and wild-type EGFR, respectively. The difference between patients with high and low abundances of EGFR mutations was not significant regarding ORR and OS.

CONCLUSION:

The relative EGFR mutation abundance could predict benefit from EGFR-TKI treatment for advanced NSCLC.

• Authors: Qing Zhou, Xu-Chao Zhang, Zhi-Hong Chen, Xiao-Lu Yin, Jin-Ji Yang, Chong-Rui Xu, Hong-Hong Yan, Hua-Jun Chen, Jian Su, Wen-Zhao Zhong, Xue-Ning Yang, She-Juan An, Bin-Chao Wang, Yi-Sheng Huang, Zhen Wang, Yi-Long Wu
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 29 Issue 24 Pg. 3316-21 (Aug 20 2011) ISSN: 1527-7755 [Electronic] United States
• PMID: 21788562 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, mortality, pathology)
• Disease-Free Survival
• ErbB Receptors (genetics)
• Female
• Gefitinib
• Humans
• Lung Neoplasms (drug therapy, genetics, mortality, pathology)
• Male
• Middle Aged
• Mutation
• Protein Kinase Inhibitors (therapeutic use)
• Quinazolines (therapeutic use)