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Epidermal growth factor receptor tyrosine kinase inhibitor-resistant disease.

ABSTRACT: PURPOSE:EGFR-mutant lung cancer was first described as a new clinical entity in 2004. Here, we present an update on new controversies and conclusions regarding the disease. METHODS:This article reviews the clinical implications of EGFR mutations in lung cancer with a focus on epidermal growth factor receptor tyrosine kinase inhibitor resistance. RESULTS:The discovery of EGFR mutations has altered the ways in which we consider and treat non-small-cell lung cancer (NSCLC). Patients whose metastatic tumors harbor EGFR mutations are expected to live longer than 2 years, more than double the previous survival rates for lung cancer. CONCLUSION:The information presented in this review can guide practitioners and help them inform their patients about EGFR mutations and their impact on the treatment of NSCLC. Efforts should now concentrate on making EGFR-mutant lung cancer a chronic rather than fatal disease.

SUBMITTER: Ohashi K

PROVIDER: S-EPMC3589701 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Epidermal growth factor receptor tyrosine kinase inhibitor-resistant disease.

Ohashi Kadoaki K Maruvka Yosef E YE Michor Franziska F Pao William W

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20130211 8

<h4>Purpose</h4>EGFR-mutant lung cancer was first described as a new clinical entity in 2004. Here, we present an update on new controversies and conclusions regarding the disease.<h4>Methods</h4>This article reviews the clinical implications of EGFR mutations in lung cancer with a focus on epidermal growth factor receptor tyrosine kinase inhibitor resistance.<h4>Results</h4>The discovery of EGFR mutations has altered the ways in which we consider and treat non-small-cell lung cancer (NSCLC). Pa ...[more]

PMID: 23401451

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Project description:The Lung Adjuvant Cisplatin Evaluation (LACE) meta-analysis and the meta-analysis of individual participant data reported by non-small cell lung cancer (NSCLC) Meta-analysis Collaborative Group in neo-adjuvant setting validated respectively that adjuvant and neoadjuvant chemotherapy would significantly improve overall survival (OS) and recurrence-free survival for resectable NSCLC. However, chemotherapy has reached a therapeutic plateau. It has been confirmed that epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) targeting therapy provides a dramatic response to patients with advanced EGFR-mutation positive NSCLC. Researchers have paid more attention to exploring applications of TKIs to early resectable NSCLCs. Several studies on adjuvant TKI treatment concluded its safety and feasibility. But there existed certain limitations of these studies as inference factors to interpret data accurately: the BR19 study recruited patients among which almost 52% had stage IB and only 15 (3.0%, 15/503) had been confirmed with EGFR-mutant type; retrospective studies performed at Memorial Sloan Kettering Cancer Center (MSKCC) selected EGFR mutant-type NSCLC patients but couldn't avoid inherent defects inside retrospective researches; the RADIANT study revised endpoints from targeting at EGFR immunohistochemistry (IHC)+ and/or fluorescence in situ hybridization (FISH)+ mutation to only EGFR IHC+ mutation, leading to selective bias; despite that the SELECT study validated efficacy of adjuvant TKI and second round of TKI after resistance occurred, a single-arm clinical trial is not that persuasive in the absence of comparison with chemotherapy. Taking all these limitations into account, CTONG1104 in China and IMPACT in Japan have been conducted and recruiting patients to offer higher level of evidences to explore efficacy of preoperative TKI therapy for early resectable EGFR mutation positive NSCLC patients (confirmed by pathological results of tumor tissue or lymph node biopsy). On the other hand, case reports and several phase II clinical trials with small sample size tried to elbow their way on respect of preoperative TKI treatment and advised that TKI tended to improve response rate. However, no data on survival rate was present. The first phase II study of biomarker-guided neoadjuvant therapy for stage IIIA-N2 NSCLC patients stratified by EGFR mutation status, sponsored by CSLC0702, showed erlotinib tended to improve response rate, but failed to show benefits of disease-free survival (DFS) or OS. Subsequently, CTONG1103 was designed to investigate efficacy of erlotinib vs. combination of gemcitabine/cisplatin (GC) as neoadjuvant treatment in stage IIIA-N2 NSCLC with sensitizing EGFR mutation in exon 19 or 21. All these ongoing trials should be worthy of our expect to provide convincing evidences for customized therapy for patients with resectable NSCLC.

Dataset Information

Epidermal growth factor receptor tyrosine kinase inhibitor-resistant disease.

Publications

Epidermal growth factor receptor tyrosine kinase inhibitor-resistant disease.

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