Expert consensus on icotinib as adjuvant therapy for non-small cell lung cancer / 中华肿瘤杂志

Clinical studies have established the clinical application of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) adjuvant targeted therapy. Compared with chemotherapy, the high efficiency and low toxicity of targeted therapy increases the survival benefit of patients. Icotinib was the first EGFR-TKI with independent intellectual property rights in China and the third EGFR-TKI to be marketed in the world. In order to summarize the experience of icotinib and other EGFR-TKIs in the adjuvant treatment of non-small cell lung cancer and further standardize and guide the clinical application of icotinib, experts from the China International Exchange and Promotive Association for Medical and Health Care and the Guangdong Association of Thoracic Diseases have organized an expert consensus on the adjuvant treatment of non-small cell lung cancer with icotinib, which is expected to provide clinicians with evidence-based medical evidences for postoperative targeted drug using.

Progress of mechanisms of osimertinib resistance and coping strategies in non-small cell lung cancer / 肿瘤研究与临床

Osimertinib, the third generation of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has demonstrated notable clinical benefit in the targeted therapy for patients with non-small cell lung cancer (NSCLC). However, the development of drug resistance is an inevitable challenge. In order to tackle this issue, ongoing efforts are being made to develop new generations of targeted drugs and treatment strategies, some of which are already undergoing clinical trials. This article aims to review the current research on the mechanisms of osimertinib resistance and outline the advancements made in post-drug resistance treatment strategies.

The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) plus radiotherapy in the treatment of lung adenocarcinoma patients with central nervous system metastases: a meta-analysiss / 中国医师杂志

Objective:To systematically evaluate the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) combined with radiotherapy in the treatment of lung adenocarcinoma with central nervous system (CNS) metastasis.Methods:PubMed, EMBASE, Medline, Cochrane Library, clinical trials and other databases were searched to collect the clinical control studies of EGFR-TKI combined with radiotherapy versus EGFR-TKI or radiotherapy alone in the treatment of lung adenocarcinoma with CNS metastasis published at home and abroad from January 2012 to April 2019. After evaluating the data, Revman 5.3 software was used for meta-analysis.Results:10 studies involving 1 379 participants were included. The results indicated that compared with EGFR-TKI or radiotherapy alone, EGFR-TKI plus radiotherapy had a significant benefit on overall response rate (ORR) [ OR: 3.81, 95% CI(1.73, 8.39); P<0.01], overall survival (OS) [ HR: 0.60, 95% CI(0.41, 0.89); P=0.01], neurological progression free survival (nPFS) [ HR: 0.65, 95% CI(0.46, 0.91); P=0.01] compared with EGFR-TKI or radiotherapy alone. Conclusions:EGFR-TKI plus radiotherapy had better ORR, OS, nPFS compared with TKI or radiotherapy alone.

Effect of almonertinib on the proliferation, invasion, and migration in non-small cell lung cancer cells / 中南大学学报(医学版)

OBJECTIVES@#Lung cancer is one of the most common malignant tumors in the world, and its lethality ranks the first among many malignant tumors. For non-small cell lung cancer (NSCLC) patients, due to the high mortality rate, the overall 5-year survival rate is less than 15%. When NSCLC undergoes local invasion, the 5-year survival rate is only 20%, and it is even lower when distant metastasis occurs up to 4%. Almonertinib is an innovative drug independently researched and developed by China with independent intellectual property rights. As an epidermal growth factor receptor tyrosine kinase inhibitor, almonertinib is mainly used for locally advanced or metastatic NSCLC patients with epidermal growth factor receptor (EGFR) T790M mutation. This study aims to investigate the effects of almonertinib on the proliferation, invasion and migration of NSCLC cells in vitro.@*METHODS@#NSCLC cells H1975 and PC-9 were cultured in vitro. The effects of almonertinib on the proliferation, apoptosis, invasion, and migration of H1975 and PC-9 cells were detected by CCK-8 assay, apoptotic assay and Transwell assay. The expression of invasion and migration related proteins was detected by Western blotting.@*RESULTS@#The CCK-8 experiment showed that almonertinib inhibited the proliferation of H1975 and PC-9 cells in a time- and dose-dependent manner. The IC@*CONCLUSIONS@#Almonertinib can inhibit the proliferation, invasion, and migration of NSCLCH1975 and PC-9 cells in vitro and vivo, and promote the apoptosis of H1975 and PC-9 cells. The underlying mechanism may be related to the inhibition of tumor cell epithelial mesenchymal transformation and metalloproteinase expression.

Clinical research and drug review of epidermal growth factor receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer / 中华肿瘤杂志

Lung cancer is the most frequently diagnosed cancer and the most common cause of cancer mortality in China. Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancers. The mutation rate of epidermal growth factor receptor (EGFR) gene is relatively high, accounts for 32%~38% of all NSCLC. During the last decade, the application of EGFR specific tyrosine kinase inhibitors (TKI) significantly improved prognosis of NSCLC patients with sensitive EGFR mutations. Thus, the research and development of third generation EGFR-TKI have entered the period of rapid development. The fourth generation EGFR-TKI which targeting EGFR C797S has even begun clinical development in China. This review will discuss the clinical research and drug review of EGFR-TKI from the perspective of drug review.

Bevacizumab Combined with Icotinib Overcomes Osimertinib Resistance in a Patient of Non-Small Cell Lung Cancer / 中国医学科学杂志(英文版)

A 61-year-old Chinese woman was diagnosed as primary pulmonary adenocarcinoma of left superior lobe with epidermal growth factor receptor (EGFR) 19 del mutation positive. Treatment with icotinib was given, but her disease progressed after 6 months remission. CT-guide needle biopsy for the new lesion in inferior lobe of left lung demonstrated intrapulmonary metastasis, and EGFR gene panel by Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR) confirmed EGFR T790M mutation. Treatment with osimertinib was initiated. After 2 months remission, the disease progressed. Re-biopsy was performed for the tumor in the inferior lobe of left lung, and ARMS-PCR demonstrated no other gene mutation except EGFR 19 del. Icotinib was re-challenged, but disease progressed continuously. Bevacizumab was added, and partial response was achieved after 2-cycle of combination therapy. The non-small cell lung cancer (NSCLC) in this case maintained EGFR activating mutation and lost EGFR T790M mutation was a genetic change after osimertinib treatment. This case suggests the re-challenge of the first-generation EGFR-TKIs combined with bevacizumab may overcome the tumor resistance and prolong survival of NSCLC patient.

Prognostic Analysis of EGFR-TKIs Combined with Gamma Knife in EGFR-mutant Lung Adenocarcinoma with Brain Metastasis / 中国肺癌杂志

BACKGROUND@#Advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma had a high overall incidence of brain metastasis during the full course, and local brain radiotherapy combined with systemic targeted therapy may be a better strategy. This study aimed to identify the prognostic factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients who received EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in combination with gamma knife radiosurgery.@*METHODS@#Retrospective analysis of EGFR-mutant lung adenocarcinoma patients with brain metastases which developed at initial diagnosis or during EGFR-TKIs treatment period were performed. Intracranial progression free survival (PFS) was statistically analyzed between different subgroups to find out the prognostic factors including gender, age, smoking history, extracranial metastasis, EGFR mutation type, size and number of intracranial lesions, carcino-embryonic antigen (CEA) level, lung-molGPA score and so on.@*RESULTS@#A total of 74 EGFR-mutant brain-metastatic lung adenocarcinoma patients were enrolled in this study, with median intracranial PFS of 14.7 months. One-year intracranial-progression-free rate was 58.5%, and two-year rate was 22.2%. Univariate survival analysis showed that patients with lower CEA level at initial diagnosis (3)(15 months vs 12.6 months, P=0.041) were prone to have a superior intracranial PFS. Multivariate analysis showed that CEA≥10 ng/mL and intracranial lesion≥2 cm were the independent risk factors of intracranial PFS.@*CONCLUSIONS@#EGFR-TKIs in combination with gamma knife radiosurgery was an efficient treatment option to control the cranial tumor lesion. CEA≥10 μg/L at initial diagnosis and intracranial lesion≥2 cm were the risk factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients receiving EGFR-TKIs in combination with gamma knife radiosurgery.

Advances in the mechanisms of acquired resistance to EGFR-tyrosine kinase inhibitors in non-small cell lung cancer / 药学学报

Lung cancer ranks the first in the mortality rate among all cancers, and non-small cell lung carcinoma (NSCLC) accounts for about 80% of the incidence of lung cancer. In recent years, the drugs targeting specific molecules have been developed rapidly. The epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have achieved good results in the treatment of patients with NSCLC. Currently, there are three generations of EGFR-TKIs, and the treatment outcome of these drugs surpasses traditional chemotherapies. However, the problems of acquired resistance remains in the course of treatment. In this review, research progress of the mechanisms of acquired resistance is divided into two parts: EGFR-dependent pathway and EGFR-independent pathway. The EGFR-dependent pathway mainly includes EGFR gene mutations, whereas the EGFR-independent pathways include HER2 amplification, BIM deletion, activation of HGF/c-Met pathway, activation of IGF1R, RAS mutation, PTEN deletion, epithelial-mesenchymal transition, PUMA loss, and high levels of expression of VEGF or IL-6. These interconnected mechanisms are linked with acquired resistance to EGFR-TKIs in NSCLC.

The efficacy and influence factors analysis of EGFR TKIs on patients with lung adenosquamous carcinoma / 中华肿瘤杂志

Objective@#To investigate the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) on patients with lung adenosquamous carcinoma, and to analyze relative factors.@*Methods@#From August 2007 to July 2017, 40 patients who were pathologically diagnosed as lung adenosquamous carcinoma in our hospital and received EGFR TKIs treatment were retrospectively analyzed. All patients underwent EGFR mutation detection, resulted in 11 wild type, 13 19Del, 13 21L858R mutations, and 3 uncommon EGFR mutations in 20 exon and 19/21 complex mutation. A higher frequency of EGFR mutation was found in non-smokers and patients with adenocarcinoma components over 50.0%.@*Results@#Twenty-six (65.0%) patients had disease progression after EGFR TKIs treatment, with a median progression-free survival (PFS) of 5.5 months (95% CI 0.52-10.49 months). A total of 20 (50.0%) patients died with an median overall survival (OS) of 15 months (95% CI 11.03-18.97 months). Multivariate analysis showed that gender, age, smoking, histopathological subtypes, EGFR mutations, and brain metastasis had no influence on PFS (all P>0.05). Gender, age, smoking, histopathological subtypes, and the presence of brain metastasis during TKI treatment had no influence on OS (P>0.05), while EGFR mutation is the only influencing factor of OS (P<0.05) in the current study.@*Conclusions@#EGFR TKIs had modest efficacy in lung adenosquamous carcinoma, especially in patients with EGFR mutation. Based on the pathological features, EGFR mutation and EGFR TKIs treatment should be introduced into the routine clinical practice to improve the survival of patients with lung adenosquamous carcinoma.

Predictive Factors for Switched EGFR-TKI Retreatment in Patients with EGFR-Mutant Non-Small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: Third-generation tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKIs) have proved efficacious in treating non-small cell lung cancer (NSCLC) patients with acquired resistance resulting from the T790M mutation. However, since almost 50% patients with the acquired resistance do not harbor the T790M mutation, retreatment with first- or second-generation EGFR-TKIs may be a more viable therapeutic option. Here, we identified positive response predictors to retreatment, in patients who switched to a different EGFR-TKI, following initial treatment failure. METHODS: This study retrospectively reviewed the medical records of 42 NSCLC patients with EGFR mutations, whose cancers had progressed following initial treatment with gefitinib or erlotinib, and who had switched to a different first-generation EGFR-TKI during subsequent retreatment. To identify high response rate predictors in the changed EGFR-TKI retreatment, we analyzed the relationship between clinical and demographic parameters, and positive clinical outcomes, following retreatment with EGFR-TKI. RESULTS: Overall, 30 (71.4%) patients received gefitinib and 12 (28.6%) patients received erlotinib as their first EGFR-TKI treatment. Following retreatment with a different EGFR-TKI, the overall response and disease control rates were 21.4% and 64.3%, respectively. There was no significant association between their overall responses. The median progression-free survival (PFS) after retreatment was 2.0 months. However, PFS was significantly longer in patients whose time to progression was ≥10 months following initial EGFR-TKI treatment, who had a mutation of exon 19, or whose treatment interval was <90 days. CONCLUSION: In patients with acquired resistance to initial EGFR-TKI therapy, switched EGFR-TKI retreatment may be a salvage therapy for individuals possessing positive retreatment response predictors.

Relationship Analysis of CYP3A4*18 Gene Polymorphism with Therapeutic Efficacy and ADR of EGFR-TKI in Advanced NSCLC Patients Receiving Primary Treatment / 中国药房

OBJECTIVE:To investigate the relationship of Cytochrome P450 (CYP)3A4* 18 gene polymorphism with therapeutic efficacy and ADR of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in non-small cell lung cancer (NSCLC) patients receiving primary treatment.METHODS:A total of 46 advanced NSCLC patients receiving primary EGFR-TKI (gefitinib or edotinib) treatment until disease progression or intolerance were selected from our hospital during Jan.2013-Mar.2016,and (gefitinib of erlotinib) treatment until disease progression or intolerance.CYP3A4*18 genotype was detected by PCR and direct sequencing.Clinical efficacies,progression-free survival (PFS) and the occurrence of ADR were compared among differ ent genotypes.RESULTS:Among 46 patients,there were 17 cases of CYP3A4*18 wild-type and 29 cases of CYP3A4*18 mutation-type,with mutation frequency of 63.0％.The objective response rate (ORR) of CYP3A4*18 wild-type patients was 23.5％,and disease control rate (DCR) of them was 70.6％.For CYP3A4*18 mutation-type patients,ORR and DCR were 27.6％ and 69.0％.There was no statistical significance in the proportion of patients with partial response,stable disease or progressive dis ease,ORR or DCR among different genotypes (P＞0.05).PFS of female patients were significantly longer than male patients;those of patients without smoking history were significantly longer than those with smoking history,with statistical significance (P＜0.05).There was no correlation between patients' age,therapy drugs,Eastern Oncology Collaboration scores,EGFR mutation types,CYP3A4*18 genotypes and PFS (P＞0.05).Patients'gender and smoking history were independent prognostic factors for PFS [odds ratios were 3.438,0.205,95％ CI were(1.393,8.488),(0.088,0.481)].Among CYP3A4* 18 wild-type patients,6 patients suffered from rash (35.3％) and 3 diarrhea (17.6％).Among mutation-type patients,26 patients suffered from rash (89.7％) and 15 diarrhea (51.7％),with statistical significance (P＜0.05).There was no statistical significance in the incidence of liver function injury and interstitial dermatitis among different genotypes (P＞0.05).CONCLUSIONS:CYP3A4*18 gene polymorphism may be not associated with therapeutic efficacy of EGFR-TKI in advanced NSCLC patients receiving primary treatment,but it is correlated with the occurrence of ADR.Mutation type patients are more likely to suffered from rash,diarrhea and other ADR.

Progress on EGFR-TKI in treatment of non-small cell lung cancer with S768I mutation / 中国肿瘤临床

Lung cancer is one of the malignant tumors with high mortality rates. In recent years, considerable progress on the treat-ment of non-small cell lung cancer has been achieved. Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) improves the median progression free survival of patients with sensitive mutations to 27.7 months. However, the therapeutic effect of EGFR-TKI on uncommon mutations remains unknown. S768I mutation is an insensitive mutation in the EGFR20 exon, and its incidence rate rang-es from 1％to 2％. In this review, the effect of different generation EGFR-TKI on single or complex S768I mutation during treatment is discussed.

Efficacy of EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer patients with uncommon EGFR 21L861Q mutation / 上海交通大学学报（医学版）

Objective· To evaluate the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) in non small cell lung cancer (NSCLC)patients with uncommon EGFR 21L861Q mutation. Methods·Between June 2011 and Marth 2015,clinical data of 21 stageⅢB/ⅣNSCLC patients who received EGFR-TKI harboring uncommon 21L861Q mutation in EGFR at the Shanghai Chest Hospital were collected.Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS ) and overall survival (OS ) of the patients under TKI therapy were retrospectively analyzed. Results · ORR and DCR of the patients under TKIs therapy (first-line+second-line+third-line) were 42.9% and 66.7% respectively. PFS and OS of patients who received therapy that consisted of EGFR-TKIs(first-line+second-line+third-line)were 7.03 months(95% CI,5.50-8.69)and 22.80 months(95% CI,16.22-25.65). Conclusion·Our post-hoc analyses demonstrated that EGFR-TKIs showed activity in patients with uncommon EGFR 21L861Q-mutant NSCLC, less effective than in those with common mutations.

The association between plasma TGF-α levels and EGFR-TKI treatment sensitivity and prognosis in NSCLC patients with EGFR mutation / 中国癌症杂志

Background and purpose: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is of advantage in treating non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, their clinical effects vary individually. This study aimed to evaluate whether the EGFR ligand, plasma transforming growth factor α (TGF-α), could act as a predictor for the EGFR-TKI treatment e?ciency in NSCLC patients with EGFR mutations and the association between TGF-α and prognosis in these patients. Methods: Seventy-five NSCLC patients with EGFR gene positive mutation were included in the current study from May 2012 to Jul. 2014 in Ruikang Hospital A?liated to Guangxi University of Chinese Medicine. Plasma TGF-α was measured using enzyme-linked immunosorbent assay (ELISA) in all of the patients before EGFR-TKI treatment. The radiographic evaluation was performed 2 months after the therapy. The association between TGF-α and clinical outcome and its prediction e?ciency were determined, followed by the further analysis of the association between TGF-α and overall survival (OS) as well as progression-free survival (PFS). Results: After EGFR-TKI treatment, there were 20 patients with partial response (PR), 25 with stable disease (SD) and 30 with progression disease (PD) in all 75 NSCLC patients harboring EGFR positive mutation. The disease control (DC) rate reached 60%. Patients in PD group presented statistically significant higher plasma TGF-αthan patients in the DC group (P<0.01). Multivariate COX model indicated that smoking status, lymph node metastasis and plasma TGF-α levels were independent risk factors for prognosis in these patients. The ROC analysis revealed that baseline plasma TGF-α showed good prediction e?ciency [area under the curve (AUC)=0.926] and the cut-off point of TGF-α was 16.75 pg/mL. Higher level of TGF-α (≥16.75 pg/mL) was associated with smoking history, clinical stage, lymph node metastasis and clinical outcome of the patients (P<0.05). In comparison to patients with low TGF-α, the patients with high TGF-α concentration presented significantly reduced median OS and PFS (log-rank P<0.05). Conclusion: Higher plasma TGF-α (≥16.75 pg/mL) had a predictive role in EGFR-TKI resistance and poor prognosis.

Utilization Investigation of EGFR-TKI in the Patients with Lung Cancer in 11 Hospitals of Zhejiang Province during 2009 and 2015 / 中国药师

Objective: To investigate the utilization status of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in 11 hospitals of Zhejiang province from 2009 to 2015, and to analyze the use rationality.Methods: The doctor's advice in 40 days annually was collected in 11 hospitals of Zhejiang province from 2009 to 2015, and the drug consumption, frequency of utilization (DDDs), defined daily cost (DDC) and drug utilization index (DUI) were analyzed for the patients with lung cancer treated with EGFR-TKI.Results: Icotinib, erlotinib and gefitinib were the three prevalent EGFR-TKIs used in Zhejiang province, and icotinib started to be used in clinics in 2013.The overall cost of EGFR-TKIs increased year by year during 2009 and 2015, and the total amount of sales increased by 4.67 times in 2015 when compared with that in 2009.Generally, the DDDs value of erlotinib showed a decreasing trend, however, that of icotinib and gefitinib rose year by year during 2009 and 2015.Erlotinib had the highest DDC followed by gefitinib and icotinib.The mean value of DUI of the three targeted drugs was about 1.Conclusion: The utilization of EGFR-TKI is reasonable in 11 hospitals of Zhejiang province with increasing comsuption.

Drug Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Non-Small Cell Lung Cancer and Coping Strategy: Discussion based on Yang Deficiency / 中医杂志

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is a kind of targeted drug for the treatment of non-small cell lung cancer (NSCLC),but almost all patients develop EGFR-TKI resistance.In Chinese medicine,it is believed that Yang deficiency is the leading cause of tumor,which could end up with the internal formation of cancer toxin and promote the formation of tangible excess pathogens.Clinical and experimental studies have shown that the Chinese medicine treatment based on Yang-warming method can inhibit EGFR-TKI resistance and improve the therapeutic effect of EGFR-TKI.The mechanism may be related to the regulation of miRNA gene and estrogen receptor expression,being against tumor heterogeneity and the regulation of tumor microenvironment.Therefore,Yang deficiency is the key pathogenesis of the EGFR-TKI resistance in NSCLC,and the method reinforcing Yang and suppressing Yin is the basic therapeutic way in Chinese medicine to overcome EGFR-TKI resistance.

Clinical trials on primary lung cancer in China: Past, present, and future / 医学研究生学报

Clinical trials play an important role in guiding clinical practice .Over the past decade , Chinese investigators on lung cancer have not only participated and gradually taken a leadership in international multi -center clinical trials , but also established the first multi-center collaborative clinical trial group in China , which has promoted the development of new anti-cancer drugs , the for-mation of new treatment strategies and the innovation of clinical trial designs .Taking epidermal growth factor receptor-tyrosine kinase inhibitors, we focus on the clinical trials on lung cancer aimed at reshaping the clinical practice strategies in China or even worldwide with the participation or leadership of Chinese researchers as well as current challenges and future prospects in lung cancer studies .

Concomitance of P-gp/LRP Expression with EGFR Mutations in Exons 19 and 21 in Non-Small Cell Lung Cancers

PURPOSE: Traditional chemotherapy is the main adjuvant therapy for the treatment of non-small cell lung cancer (NSCLC). However, the emergence of multi-drug resistance (MDR) has greatly restricted the curative effect of chemotherapy. Therefore, it is necessary to find a method to treat MDR NSCLC clinically. It is worth investigating whether NSCLCs that are resistant to traditional chemotherapy can be effectively treated with tyrosine kinase inhibitors targeting epidermal growth factor receptor (EGFR). MATERIALS AND METHODS: The expression of P-glycoprotein (P-gp) and lung resistance-related protein (LRP) was detected by immunohistochemistry, and mutations in EGFR (exons 19 and 21) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (exon 2) were detected by high-resolution melting analysis (HRMA) of surgical NSCLC specimens from 127 patients who did not undergo traditional chemotherapy or radiotherapy. A Pearson chi-square test was performed to analyze the correlations between the expression of P-gp and LRP and mutations in EGFR and KRAS. RESULTS: The expression frequencies of P-gp and LRP were significantly higher in adenocarcinomas from non-smoking patients; the expression frequency of LRP was significantly higher in cancer tissue from female patients. The frequency of EGFR mutations was significantly higher in well to moderately differentiated adenocarcinomas from non-smoking female patients. The frequency of EGFR mutations in the cancers that expressed P-gp, LRP, or both P-gp and LRP was significantly higher than that in cancers that did not express P-gp or LRP. CONCLUSION: NSCLCs expressing P-gp/LRP bear the EGFR mutation in exon 19 or 21 easily.

Nutritional status in the era of target therapy: poor nutrition is a prognostic factor in non-small cell lung cancer with activating epidermal growth factor receptor mutations

BACKGROUND/AIMS: Pretreatment nutritional status is an important prognostic factor in patients treated with conventional cytotoxic chemotherapy. In the era of target therapies, its value is overlooked and has not been investigated. The aim of our study is to evaluate the value of nutritional status in targeted therapy. METHODS: A total of 2012 patients with non-small cell lung cancer (NSCLC) were reviewed and 630 patients with activating epidermal growth factor receptor (EGFR) mutation treated with EGFR tyrosine kinase inhibitor (TKI) were enrolled for the final analysis. Anemia, body mass index (BMI), and prognostic nutritional index (PNI) were considered as nutritional factors. Hazard ratio (HR), progression-free survival (PFS) and overall survival (OS) for each group were calculated by Cox proportional analysis. In addition, scores were applied for each category and the sum of scores was used for survival analysis. RESULTS: In univariable analysis, anemia (HR, 1.29; p = 0.015), BMI lower than 18.5 (HR, 1.98; p = 0.002), and PNI lower than 45 (HR, 1.57; p < 0.001) were poor prognostic factors for PFS. Among them, BMI and PNI were independent in multi-variable analysis. All of these were also significant prognostic values for OS. The higher the sum of scores, the poorer PFS and OS were observed. CONCLUSIONS: Pretreatment nutritional status is a prognostic marker in NSCLC patients treated with EGFR TKI. Hence, baseline nutritional status should be more carefully evaluated and adequate nutrition should be supplied to these patients.

Application of EGFR-TKI in locally advanced non-small cell lung cancer / 国际肿瘤学杂志

With the deepening of the lung cancer molecular biology research,small molecular targets antitumor drugs make breakthrough progress,the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is one of the most attention drug.A series studies show that EGFR-TKI can enhance the antitumor activity of ionizing radiation.Therefore,EGFR-TKI combined with radiotherapy alone for poor-risk patients appears survival benefit,but can't ignore the lung toxicity.However,there is a big contro-versy that EGFR-TKI combined with chemoradiotherapy for locally advanced NSCLC.