Distinct clinical outcomes of non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations treated with EGFR tyrosine kinase inhibitors: non-responders versus responders

• Published in: PloS one Vol. 8; no. 12; p. e83266
• Main Authors: Hsiao, Shih-Hsin, Liu, H Eugene, Lee, Hsin-Lun, Lin, Chii-Lan, Chen, Wei-Yu, Wu, Zhung-Han, Lin, Sey-En, Chiang, Ling-Ling, Chung, Chi-Li
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.12.2013; Public Library of Science (PLoS)
• Subjects: Aged; Aged, 80 and over; Biomarkers; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Care and treatment; Cell survival; Chemotherapy; Clonal deletion; Confidence intervals; Drug development; Epidermal growth factor; Epidermal growth factor receptors; Epidermal growth factors; Exons; Female; Genetic aspects; Hospitals; Humans; Inhibitors; Internal medicine; Lung cancer; Lung diseases; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Medical research; Medicine; Middle Aged; Multivariate analysis; Mutation; Non-small cell lung cancer; Non-small cell lung carcinoma; Oncology; Pathology; Patient outcomes; Patients; Phenols (Class of compounds); Prognosis; Protein Kinase Inhibitors - therapeutic use; Protein-tyrosine kinase; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Respiratory therapy; Retrospective Studies; Studies; Survival; Survival Analysis; Treatment Outcome; Tumors; Tyrosine; Tyrosine kinase inhibitors; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0083266

Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been associated with favorable progression free survival (PFS) in patients with non-small cell lung cancers (NSCLC) harboring EGFR mutations. However, a subset of this population doesn't respond to EGFR-TKI treatment. Therefore, the present study aimed to elucidate survival outcome in NSCLC EGFR-mutant patients who were treated with EGFR TKIs. Among the 580 consecutive NSCLC patients who were treated at our facility between 2008 and 2012, a total of 124 treatment-naïve, advanced NSCLC, EGFR-mutant patients treated with EGFR TKIs were identified and grouped into non-responders and responders for analyses. Of 124 patients, 104 (84%) responded to treatment, and 20 (16%) did not; and the overall median PFS was 9.0 months. Notably, the PFS, overall survival (OS) and survival rates were significantly unfavorable in non-responders (1.8 vs. 10.3 months, hazard ratio (HR) = 29.2, 95% confidence interval (CI), 13.48-63.26, P<0.0001; 9.4 vs. 17.3 months, HR = 2.74, 95% CI, 1.52-4.94, P = 0.0008; and 58% vs. 82% in 6, 37% vs. 60% in 12, and 19 vs. 40% at 24 months, respectively). In multivariate analysis, treatment efficacy strongly affected PFS and OS, independent of covariates (HR = 47.22, 95% CI, 17.88-124.73, P<0.001 and HR = 2.74, 95% CI, 1.43-5.24, P = 0.002, respectively). However, none of the covariates except of the presence of EGFR exon 19 deletion in the tumors was significantly associated with better treatment efficacy. A subset of NSCLC EGFR-mutant patients displayed unfavorable survival despite EGFR TKI administration. This observation reinforces the urgent need for biomarkers effectively predicting the non-responders and for drug development overcoming primary resistance to EGFR TKIs. In addition, optimal therapeutic strategies to prolong the survival of non-responders need to be investigated.