Complex Mutations in the Epidermal Growth Factor Receptor Gene in Non-small Cell Lung Cancer

Hata, Akito; Yoshioka, Hiroshige; Fujita, Shiro; Kunimasa, Kei; Kaji, Ryuji; Imai, Yukihiro; Tomii, Keisuke; Iwasaku, Masahiro; Nishiyama, Akihiro; Ishida, Tadashi; Katakami, Nobuyuki

doi:10.1097/jto.0b013e3181e8b3c5

Cited by 79 publications

(80 citation statements)

References 26 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A retrospective study which investigated the frequency of complex mutations in 783 NSCLC patients found the majority was G719S plus L858R mutation (n = 8), the result also suggested poor response to gefitinib in patients with G719S plus L858R mutation [36]. Besides, previous studies revealed that patients with exon 18 (G719S) plus L858R mutation showed poor outcomes with gefitinib [37], [38], [39].…”

Section: Discussionmentioning

confidence: 99%

Patients with Exon 19 Deletion Were Associated with Longer Progression-Free Survival Compared to Those with L858R Mutation after First-Line EGFR-TKIs for Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

et al. 2014

View full text Add to dashboard Cite

BackgroundsIt has been extensively proved that the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is superior to that of cytotoxic chemotherapy in advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, the question of whether the efficacy of EGFR-TKIs differs between exon 19 deletion and exon 21 L858R mutation has not been yet statistically answered.MethodsSubgroup data on hazard ratio (HR) for progression-free survival (PFS) of correlative studies were extracted and synthesized based on random-effect model. Comparison of outcomes between specific mutations was estimated through indirect and direct methods, respectively.ResultsA total of 13 studies of advanced NSCLC patients with either 19 or 21 exon alteration receiving first-line EGFR-TKIs were included. Based on the data from six clinical trials for indirect meta-analysis, the pooled HRTKI/chemotherapy for PFS were 0.28 (95% CI 0.20–0.38, P<0.001) in patients with 19 exon deletion and 0.47 (95% CI 0.35–0.64, P<0.001) in those with exon 21 L858R mutation. Indirect comparison revealed that the patients with exon 19 deletion had longer PFS than those with exon 21 L858R mutation (HR19 exon deletion/exon 21 L858R mutation = 0.59, 95% CI 0.38–0.92; P = 0.019). Additionally, direct meta-analysis showed similar result (HR19 exon deletion/exon 21 L858R mutation = 0.75, 95% CI 0.65 to 0.85; P<0.001) by incorporating another seven studies.ConclusionsFor advanced NSCLC patients, exon 19 deletion might be associated with longer PFS compared to L858 mutation at exon 21 after first-line EGFR-TKIs.

show abstract

Section: Discussionmentioning

confidence: 99%

Patients with Exon 19 Deletion Were Associated with Longer Progression-Free Survival Compared to Those with L858R Mutation after First-Line EGFR-TKIs for Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Relevant references from the searched studies (6 references) were also reviewed. In total, 18 patients with EGFR Del-19 + L858R mutations that received EGFR-TKIs were identified between January 2002 and January 2015 (Table I) (17)(18)(19)(20)(21)(22). Of these 18, 16 patients were assessed based on RECIST (15) and 2 patients were not evaluated.…”

Section: Discussionmentioning

confidence: 99%

EGFR-tyrosine kinase inhibitor treatment in a patient with advanced non-small cell lung cancer and concurrent exon 19 and 21 EGFR mutations: A case report and review of the literature

Yang

Zhang

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Abstract. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are considered to be effective treatments for advanced non-small cell lung cancer (NSCLC) patients with sensitizing EGFR mutations, including exon 19 deletion and exon 21 L858R mutations. However, with the development of EGFR mutation detection assays, patients with complex EGFR mutations are emerging, and their response to EGFR-TKIs remains unclear. The present study reports a case of a 62-year-old, non-smoking female patient with advanced NSCLC, presenting with concurrent EGFR 19+21 sensitizing mutations, who had a poor response to the first-line EGFR-TKI erlotinib and succumbed 5 months subsequent to diagnosis. Furthermore, the present study performed a literature review, and 18 patients with complex EGFR 19+21 mutations that had received EGFR-TKIs were identified. The majority of these patients responded well to EGFR-TKIs. To the best of our knowledge, the present case is the first to report a patient with lung adenocarcinoma with complex EGFR 19+21 sensitizing mutations that had a poor clinical response to a first-line EGFR-TKI. Despite the 70% response rate of sensitizing EGFR-mutant NSCLCs to EGFR-TKIs, there is still a proportion of patients that experience de novo resistance, and heterogeneity is likely to be important in this resistance mechanism. Therefore, comprehensive genomic detection assays and multi-targeted therapies for patients with NSCLC with complex EGFR mutations require additional investigation.

show abstract

“…According to Wu et al (21) the mutation rate of the EGFR gene in women and men was 42.9 and 23.1%, respectively. In this study, the mutation rate in female patients was 68.42%, which was higher compared with that in male patients (37.5%), with a statistically significant difference (P<0.05) (10,18,19,21). The degree of differentiation of the tumor was an important index for assessing malignant potential and prognosis.…”

Section: Discussionmentioning

confidence: 87%

“…EGFR acts on the cell signal transduction pathway, promotes the differentiation and proliferation of tumor cells, promotes tumor angiogenesis and metastasis and inhibits apoptosis (14)(15)(16). Multiple studies have proven that customized therapy significantly improved the survival rate and life quality of EGFR-positive lung cancer patients (17,18). With the improved understanding of the process of tumor pathogenesis and of the effects of EGFR gene mutation on tumor characteristics, targeted therapy has become increasingly more important, perfected and normalized (15).…”

Section: Discussionmentioning

confidence: 99%

Epidermal growth factor receptor gene mutation status and its association with clinical characteristics and tumor markers in non-small-cell lung cancer patients in Northwest China

Abdurahman

Anwar

Turghun

et al. 2015

Molecular and Clinical Oncology

View full text Add to dashboard Cite

Abstract. This study was conducted to investigate the mutation status of epidermal growth factor receptor (EGFR) and its association with clinical characteristics and tumor markers in non-small-cell lung cancer (NSCLC) patients from the Xinjiang Uygur Autonomous Region in China. We enrolled 51 cases of NSCLC patients who received radical surgical treatment in the First Affiliated Hospital of Xinjiang Medical University. Quantitative polymerase chain reaction was applied to detect exons 18, 19, 20 and 21 of the EGFR gene in tumor tissues. Multiple tumor markers, including carcinoembryonic antigen (CEA), were assessed preoperatively. The EGFR-positive rate was 49.02% (25/51), with a mutation rate of 8% (2/25) in exon 18, 52% (13/51) in exon 19, 40% (10/51) in exon 21 and no mutations in exon 20. The positive mutation rate in men and women was 37.5% (12/32) and 68.42%, respectively (13/19), with a statistically significantly higher rate in women (P<0.05). There were also statistically significant differences among adenocarcinoma, adenosquamous carcinoma and squamous cell carcinoma cases (P<0.05), while no statistically significant differences were observed in adenocarcinoma cases regarding degree of differentiation, lymph node metastasis and TNM stage (P>0.05). There was a statistically significant association between the EGFR gene mutation status and the preoperative serum CEA level (P<0.05). The mutation rate of the EGFR gene was 68.42% in female lung adenocarcinoma patients, which supports the application of targeted therapy in such cases. However, whether it is possible to obtain information regarding targeted therapy through measuring the level of serum CEA for NSCLC patients with unknown EGFR mutation status requires further investigation through related studies including a higher number of cases. IntroductionLung cancer is one of the most common malignant tumors in humans, with an equally high incidence in men and in women. Approximately 80% of lung cancer cases are non-small-cell lung cancer (NSCLC) (1). The majority of the patients present with advanced-stage lung cancer at diagnosis, when radical excision is no longer feasible (2) and the remaining treatment options include radiotherapy, chemotherapy and immune therapy. The rate of response to radiotherapy and chemotherapy is only 15-35%, which may not effectively improve the survival rate and life quality of the patients. Therefore, the total 5-year survival rate of lung cancer patients is only ~15% (2-4).Over the last few years, genetic testing and targeted therapy based on epidermal growth factor receptor (EGFR) gene mutation status has attracted significant attention. Multiple clinical studies indicated that tyrosine kinase inhibitors (TKIs) have effectively extended the survival time and improved the life quality of NSCLC patients (5), with a total effectiveness rate of >70%. However, the effectiveness rate of TKI treatment for wild-type EGFR cancers is only 10-15% (6). Therefore, it is crucial to determine the mutation status of the EGFR gene in NSC...

show abstract

Complex Mutations in the Epidermal Growth Factor Receptor Gene in Non-small Cell Lung Cancer

Abstract: Complex EGFR mutations are not rare. Gefitinib has different efficacy according to the type of complex EGFR mutations. Patients with Del-19 and L858R mutations may benefit more from gefitinib than other types of complex mutations.

Cited by 79 publications

References 26 publications

Patients with Exon 19 Deletion Were Associated with Longer Progression-Free Survival Compared to Those with L858R Mutation after First-Line EGFR-TKIs for Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

Patients with Exon 19 Deletion Were Associated with Longer Progression-Free Survival Compared to Those with L858R Mutation after First-Line EGFR-TKIs for Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

EGFR-tyrosine kinase inhibitor treatment in a patient with advanced non-small cell lung cancer and concurrent exon 19 and 21 EGFR mutations: A case report and review of the literature

Epidermal growth factor receptor gene mutation status and its association with clinical characteristics and tumor markers in non-small-cell lung cancer patients in Northwest China

Contact Info

Product

Resources

About