EGFR基因突变在非小细胞肺癌患者脑转移放疗疗效预测中的价值

目的探究表皮生长因子受体(EGFR)基因突变在非小细胞肺癌(NSCLC)患者脑转移放疗疗效预测中的价值。方法收集60例NSCLC脑转移患者临床资料,依照NSCLC患者脑转移放疗疗效分为疗效良好组(49例)和疗效不良组(11例)。比较不同放疗疗效患者的基础资料、EGFR基因突变情况及EGFR血浆含量;分析NSCLC脑转移放疗疗效的影响因素,评估EGFR基因突变及其他影响因素对NSCLC患者脑转移放疗疗效的预测价值。结果2组性别、年龄、吸烟状况、脑转移数目、卡氏评分比较,差异无统计学意义(P>0.05);2组淋巴结转移、肿瘤分期差异有统计学意义(P<0.05)。疗效良好组EGFR基因突变率(53.06%)高于疗效不良组(18.18%),差异有统计学意义(χ^(2)=5.307,P=0.021)。疗效良好组EGFR表达水平低于疗效不良组,差异有统计学意义(t=2.376,P=0.021)。将NSCLC脑转移放疗疗效作为因变量,EGFR基因突变、淋巴结转移、肿瘤分期作为自变量,进行逻辑回归分析,结果显示,EGFR基因突变是NSCLC患者脑转移放疗疗效的保护因素,淋巴结转移、肿瘤分期Ⅲ~Ⅳ期、EGFR高水平是NSCLC患者脑转移放疗疗效的危险因素。四者联合预测NSCLC脑转移放疗疗效良好的公式为Log(P)=-2.849×EGFR基因突变+2.192×淋巴结转移+1.388×肿瘤分期+1.658×EGFR水平-2.062。ROC曲线分析结果显示,EGFR基因突变对NSCLC患者脑转移放疗疗效良好的预测价值良好,灵敏度为0.818,特异度为0.610,AUC为0.714,EGFR基因突变、淋巴结转移、肿瘤分期、EGFR水平联合对NSCLC患者脑转移放疗疗效的预测价值相对单一指标较好,灵敏度、特异度较高。结论EGFR基因突变可能与NSCLC患者脑转移放疗疗效有关。EGFR基因突变与淋巴结转移、肿瘤分期、EGFR水平联合对NSCLC患者脑转移放疗疗效有良好的预测价值,EGFR基因突变可能成为临床上预测NSCLC脑转移放疗疗效的一个评价因子。

Clinical outcomes of EGFR-TKI treatment and genetic heterogeneity in lung adenocarcinoma patients with EGFR mutations on exons 19 and 21

Background:Epidermal growth factor receptor(EGFR) mutations,including a known exon 19 deletion(19 del) and exon 21 L858 R point mutation(L858R mutation),are strong predictors of the response to EGFR tyrosine kinase inhibitor(EGFR-TKI) treatment in lung adenocarcinoma.However,whether patients carrying EGFR 19 del and L858 R mutations exhibit different responsiveness to EGFR-TKls and what are the potential mechanism for this difference remain controversial.This study aimed to investigate the clinical outcomes of EGFR-TKI treatment in patients with EGFR 19 del and L858 R mutations and explore the genetic heterogeneity of tumors with the two mutation subtypes.Methods:Of 1127 patients with advanced lung adenocarcinoma harboring EGFR 19 del or L858 R mutations,532 received EGFR-TKI treatment and were included in this study.EGFR 19 del and L858 R mutations were detected by using denaturing high-performance liquid chromatography(DHPLC).T790 M mutation,which is a common resistant mutation on exon 20 of EGFR,was detected by amplification refractory mutation system(ARMS).Next-generation sequencing(NGS) was used to explore the genetic heterogeneity of tumors with EGFR 19 del and L858 R mutations.Results:Of the 532 patients,319(60.0%) had EGFR 19 del,and 213(40.0%) had L858 R mutations.The patients with EGFR 19 del presented a significantly higher overall response rate(ORR) for EGFR-TKI treatment(55.2%vs.43.7%,P = 0.017) and had a longer progression-free survival(PFS) after first-line EGFR-TKI treatment(14.4 vs.11.4 months,P = 0.034) compared with those with L858 R mutations.However,no statistically significant difference in overall survival(OS) was observed between the two groups of patients.T790 M mutation status was analyzed in 88 patients before EGFR-TKI treatment and 134 after EGFR-TKI treatment,and there was no significant difference in the co-existence of T790 M mutation with EGFR 19 del and L858 R mutations before EGFR-TKI treatment(5.6%vs.8.8%,P = 0.554)or after treatment(24.4%vs.35.4%,P = 0.176).In addition,24 patients with EGFR 19 del and 19 with L858 R mutations were analyzed by NGS,and no significant difference in the presence of multiple somatic mutations was observed between the two genotypes.Conclusions:Patients with EGFR 19 del exhibit longer PFS and higher ORR compared with those with L858 R mutations.Whether the heterogeneity of tumors with EGFR 19 del and L858 R mutations contribute to a therapeutic response difference needs further investigation.

Uncommon EGFR mutations in a cohort of Chinese NSCLC patients and outcomes of first-line EGFR-TKIs and platinum-based chemotherapy

Objective： Data on the clinical activity of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in patients with non-small-cell lung cancer （NSCLC） and uncommon EGFR mutations remain insufficient. This study aimed to investigate the effect of first-line EGFR-TKIs or platinum-based chemotherapy in NSCLC patients with uncommon EGFR mutations. Methods： We retrospectively enrolled 504 patients with EGFR-mutant NSCLC. The clinical characteristics and treatment outcomes were collected and compared between patients with common and uncommon EGFR-mutant NSCLC. Results： Seventy patients （13.9%） harboring uncommon EGFR mutations were included. Thirty of these patients received EGFR-TKIs and 40 received platinum-based chemotherapy as first-line therapy. The objective response rate （ORR） and median progression-free survival （mPFS） of patients treated with TKIs in the uncommon mutation group was significantly inferior to that in the common mutation group （ORR： 23.3% vs. 51.8%, P=0.003; mPFS： 7.1 vs. 10.9 months, P〈0.001）. In the uncommon group, mPFS was similar between first-line EGFR-TKIs treatment and platinum-based chemotherapy （7.1 vs. 6.1 months, P=0.893）. In patients with EGFR G719X or L861Q mutations, the mPFS was longer in the first-line EGFR-TKIs treatment group than in the chemotherapy group, but the difference was not statistically significant （G719X： 8.2 vs. 5.8 months, P=0.061; L861Q： 7.6 vs. 4.1 months, P=0.872）. Multivariate analyses identified adenocarcinoma （P=0.003） as the independent predictive factor for PFS in patients with uncommon EGFR mutations who were treated with first-line EGFR-TKIs. Conclusions： The current study demonstrated that the effect of first-line EGFR-TKIs was similar to that of platinum-based chemotherapy in patients with uncommon EGFR-mutant NSCLC. Adenocarcinoma was the independent predictive factor for PFS in uncommon EGFR-mutant NSCLC patients treated with first-line EGFR- TKIs.

Brain metastasis in non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations： a report of seven cases and literature review

Brain metastasis(BM)arising from non-small cell lung cancer(NSCLC)with rare epidermal growth factor receptor(EGFR)mutations is quite rare.The prognosis and therapeutic effects of BM remain enigmatic.To the best of our knowledge,this is the first report to make a separate analysis of BM from NSCLC patients with original uncommon EGFR mutations.We retrospectively reviewed 7 cases of BM arising from 42 cases of uncommon EGFR mutated lung cancer in Tianjin Medical University Cancer Institute and Hospital.We also performed a literature review to assess therapeutic features and outcomes.

Comparison of Effectiveness of Gefitinib, Erlotinib, and Afatinib in Advanced Non-small Cell Lung Cancer Patients with EGFR Mutation Positive in Indonesian Population

Background and objective EGFR-tyrosine kinase inhibitors(EGFR-TKIs) were used to treat non-small cell lung cancer(NSCLC) patients with EGFR mutation positive. This study aims to compare the effectiveness of first line TKIs;gefitinib, erlotinib, and afatinib in the treatment of advanced stage NSCLC patients with EGFR mutation positive in the Indonesian population.Methods A retrospective cohort study of 88 NSCLC patients with EGFR mutation positive treated with gefitinib(n=59), erlotinib(n=22), and afatinib(n=7) was performed in national cancer hospital in Indonesia.Inclusion criteria were stage IIIb or IV NSCLC with adenocarcinoma subtype. Subjects less than 18 years or with a history of other malignancy were excluded. Outcomes were treatment response, progression-free survival(PFS), and mortality rate. Results Complete response, partial response, and stable disease were shown in 1.1%, 35.2%, and 31.8% of subjects, respectively. There were 31.8% of subjects developed progressive disease during treatment. Regarding EGFR mutation positive profile, a total of 56.8% subjects had deletion in exon 19, 42% subjects had mutation in exon 21, and rare mutation in exon 18 was found in 3.4% of total subjects. Demography and clinical characteristics had no significant association with the risk of progressive disease. The median PFS of subjects was 11 months(95%CI: 6.8-15.2 months). There was no statistical difference of PFS between treatment groups.Conclusion Gefitinib, erlotinib, and afatinib have similar effectiveness in advanced stage NSCLC with EGFR mutation positive. Afatinib tends to be associated with longer PFS but further investigation is required.

Identification of EGFR kinase domain mutations among lung cancer patients in China:implication for targeted cancer therapy

Lung cancer is one of the leading causes of death with one of the lowest survival rates. However, a subset of lung cancer patients who are of Asian origin and carry somatic mutations in epidermal growth factor receptor or EGFR have responded remarkable well to two tyrosine kinase inhibitors, gefitinib and erlotinib. While EGFR mutation profiles have been reported from Japan, South Korea, and Taiwan, there is no such report from mainland of China where the largest pool of patients reside. In this report, we identified ten somatic mutations from a total of 41 lung cancer patients in China. Among them, seven mutations were found in 17 adenocarcinomas. In contrast to previous reports, eight of these mutations are deletions in exon 19 and two of these deletions are homozygous. These results suggest that a large portion of Chinese adenocarcinoma patients could benefit from gefitinib or erlotinib. This unique mutation profile provides a rationale to develop the next generation of EGFR inhibitors more suitable for the Chinese population.

Low Correspondence of EGFR Mutations in Tumor Tissue And Paired Serum of Non-Small-Cell Lung Cancer Patients

Objective： Epidermal growth factor receptor （EGFR） mutations are strong determinants of tumor response to EGFR tyrosine kinase inhibitors in non-small-cell lung cancer （NSCLC） patients. The aim of this study was to evaluate the correspondence between EGFR mutations in non-small-cell lung cancer tissues and in circulating DNA. Methods： The research was conducted in 50 non-small-cell lung cancer patients who had undergone curative surgery, and in whom both serum and neoplastic tissues were available. Meanwhile sera of 33 cases of advanced NSCLC patients were also analyzed. DNA were extracted from each sample. Mutations of EGFR in exonl8-21 were examined by PCR amplification method and direct sequencing. Results： EGFR mutations were detected in 15 （30%） of 50 neoplastic tissue samples, 6 cases were in-frame deletion del E746-A750 in exonl9, 9 cases were substitution in exon 21 （all were L858R except one was L861Q）, but no mutated DNA resulted in paired serum circulating DNA samples of 50 resectable patients. As the 33 advanced NSCLC patients, EGFR mutations were detected in only 2 serum circulating DNA samples, all were L858R mutation in exon 21. Conclusion： These data indicated that it was difficult to identify EGFR mutations in circulating DNA of NSCLC patients. The use of EGFR mutation in serum as a clinical method for decision making of TKI therapy is unsatisfactory.

Identifying EGFR-Expressed Cells and Detecting EGFR Multi-Mutations at Single-Cell Level by Microfluidic Chip

EGFR mutations companion diagnostics have been proved to be crucial for the efficacy of tyrosine kinase inhibitor targeted cancer therapies. To uncover multiple mutations occurred in minority of EGFR-mutated cells,which may be covered by the noises from majority of unmutated cells, is currently becoming an urgent clinical requirement. Here we present the validation of a microfluidic-chip-based method for detecting EGFR multimutations at single-cell level. By trapping and immunofluorescently imaging single cells in specifically designed silicon microwells, the EGFR-expressed cellswere easily identified. By in situ lysing single cells, the cell lysates of EGFR-expressed cells were retrieved without cross-contamination. Benefited from excluding the noise from cells without EGFR expression, the simple and cost-effective Sanger's sequencing, but not the expensive deep sequencing of the whole cell population, was used to discover multi-mutations. We verified the new method with precisely discovering three most important EGFR drugrelated mutations from a sample in which EGFR-mutated cells only account for a small percentage of whole cell population. The microfluidic chip is capable of discovering not only the existence of specific EGFR multi-mutations,but also other valuable single-cell-level information: on which specific cells the mutations occurred, or whether different mutations coexist on the same cells. This microfluidic chip constitutes a promising method to promote simple and cost-effective Sanger's sequencing to be a routine test before performing targeted cancer therapy.

Efficacy of third-line pemetrexed monotherapy versus pemetrexed combination with bevacizumab in patients with advanced EGFR mutation-positive lung adenocarcinoma

Objective： The purposes of this study were to observe the effects of different treatment strategies, including third-line pemetrexed alone versus its combination with bevacizumab, in patients with advanced epidermal growth factor receptor（EGFR） mutation-positive lung adenocarcinoma, and to analyze the effects of the different medication orders of first- and second-line drugs on third-line efficacy.Patients and methods： One hundred and sixteen cases of patients with EGFR-positive lung adenocarcinoma who had received third-line pemetrexed alone or in combination with bevacizumab between March 2010 and March 2014 at Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital of Guangzhou Medical University were analyzed retrospectively. Additionally, all the patients were treated with first-line gemcitabine and cisplatin（GP） chemotherapy and second-line EGFR tyrosine kinase inhibitor（TKI） or with first-line EGFR-TKI and second-line GP chemotherapy.Results： The median survival of 61 cases with third-line pemetrexed monotherapy was 36.22 months, the median survival time of 55 cases with third-line pemetrexed plus bevacizumab was 38.76 months, and there was a significant difference in survival time between the two groups（P=0.04）. Subgroup analysis revealed that among the 55 cases with third-line bevacizumab plus pemetrexed treatment, the median survival of 29 patients with first-line GP and second-line EGFR-TKI was 42.80 months, while the median survival of 26 patients with first-line EGFR-TKI and second-line GP was only 34.46 months; additionally, there was a significant difference in the survival time between the two subgroups（P=0.001）. Among 61 cases with thirdline pemetrexed treatment, the median survival of 34 patients with first-line GP and second-line EGFR-TKI was 38.72 months, while the median survival of 27 patients with first-line EGFR-TKI and second-line GP was only 32.94 months; the survival time of the two subgroups was significantly different（P=0.001）.Conclusions： Regardless of the order of the first- and second-line chemotherapy and TKI therapy, the pemetrexed plus bevacizumab regimen was superior to the pemetrexed monotherapy as the third-line therapy in patients with advanced EGFR-positive lung adenocarcinoma. However, this strategy is worth further investigation in prospective studies.

Mutation Analysis of EGFR Gene in Patients with Non-Small Cell Lung Cancer in Xinjiang

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) that links extracellular signals to the control of cell survival, growth, proliferation and differentiation. EGFR has been a therapeutic target for human malignancies, due to its frequent hyperactivation, therefore, it is necessary to investigate the characteristics of EGFR mutation, and identify patients who are likely to benefit from EGFR mutation. In this study, we examined 766 non-small cell lung cancer (NSCLC) patients (675 tissue, 83 thoracic water precipitation and 8 plasma samples) tested in pathology department of First Affiliated Hospital of Xinjiang Medical University from 2013 to 2017 by using ARMS-PCR method. The correlation between EGFR mutations and clinical pathological features was further explored. Subgroup analyses according to ethnicity, histological type, sample type, and tumour grade were done. Subgroup analyses showed the mutation rate of tumor tissue, thoracic water precipitation and plasm was 30.5%, 37.3%, 50.0% respectively. We found female (p < 0.0001), no smoking (p < 0.001), adenocarcinoma (p < 0.0001), and tissue specimens (Tobacco use) were associated with higher EGFR mutation rate. The most common mutations were exon 19 deletions (47.30%) and L858R point (42.32%) mutation. We have not found any differences between EGFR mutations and ethnic groups especially. In addition, we did not find differences in common mutations and rare sensitive mutations in the survival of targeted therapies.

Investigation of therapeutic modalities of G719X, an uncommon mutation in the EGFR gene in non-small cell lung cancer

Objective G719 X is the most frequently seen uncommon mutation of the epidermal growth factor receptor(EGFR) gene, which is a point mutation at exon 18 with three common subtypes, G719 A/G719 C/G719 S. This study explored the clinicopathological characteristics of the G719 X mutation and investigated the efficacy of EGFR-tyrosine kinase inhibitor(TKI) treatment and chemotherapy in patients with the G719 X mutation; the survival rate after these different treatment modalities were then analyzed in order to provide evidence for clinical treatment.Methods Clinical data of 41 patients with the G719 X mutation admitted in the Beijing Chest Hospital, Capital Medical University from September 2014 to July 2018, were collected and the EGFR mutations were detected by amplification refractory mutation system-polymerase chain reaction(ARMS-PCR). The clinicopathological characteristics of the G719 X mutation were analyzed, and the relationship among the G719 X mutation, the efficacy of different treatment modalities, and the progression-free survival(PFS) was analyzed. Results Of the 41 cases, 24(58.5%) were G719 X single mutations and 17(41.5%) were compound mutations, including G719 X/S768 I, G719 X/L861 Q, G719 X/19 del, and G719 X/c-Met compound mutation. The objective response rate(ORR) of first-line EGFR-TKI therapy was 50%(6/12), the disease control rate(DCR) was 83.3%(10/12), and the median PFS(mPFS) was 9 months. After resistance to EGFR-TKI in the previous treatment, the ORR(71.4%, 5/7) and DCR(100%, 7/7) were still high following EGFR-TKIs, by an mPFS of 8 months. The ORR of chemotherapy was 33.3%(2/6), the DCR was 100%(6/6), and the mPFS was 6 months. Conclusion G719 X is an uncommon mutation of the EGFR gene and is sensitive to many EGFR-TKIs. It can be treated with the second-or third-generation EGFR-TKIs after resistance to the first-generation EGFR-TKIs. G719 X mutation also showed favorable effect to chemotherapy.

Is EGFR gene mutation testing necessary in smokers with non-small cell lung cancer?

Objective Previous studies have proven that cumulative smoking dose predicts the prevalence of epidermal growth factor receptor(EGFR) mutations. The aim of this study was to investigate the relationship between smoking-related factors and EGFR mutation status. Methods Samples were collected from 195 smokers with non-small cell lung cancer(NSCLC) who underwent surgical resection and the presence of EGFR mutations(exons 19 and 21) were determined by real-time polymerase chain reaction(RT-PCR).Results EGFR gene mutations were present in 33(16.9%) patients who were smokers; the patients were divided into three groups according to the smoking index(SI). The incidence of EGFR mutations decreased from 38.9% in mild smokers to 8.1% in severe smokers(P = 0.001). Compared to daily smoking dose(P = 0.547), initial smoking age(P = 0.085) and duration of smoking history had a larger effect on EGFR mutation status(P = 0.002).Conclusion Although there is a decrease in the incidence of mutations with increasing SI, there were still around 17% of smokers with NSCLC that harbored EGFR mutations, so it is necessary to test for EGFR mutation status in smokers with NSCLC.

Efficacy Differences of First-line EGFR-TKIs Alone vs in Combination with Chemotherapy in Advanced Lung Adenocarcinoma Patients with Sensitive EGFR Mutation and Concomitant Non-EGFR Genetic Alterations

Background and objective:Epidermal growth factor receptor(EGFR)mutations are often associated with non-EGFR genetic alterations,which maybe a reason for the poor efficacy of EGFR tyrosine kinase inhibitors(TKIs).Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations.Materials and methods:Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant nonEGFR genetic alterations were retrospectively collected.And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy.Demographic,clinical and pathological data were collected,and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression.Survival data were obtained through face-to-face or telephone follow-up.The differences between the two groups in objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS)and overall survival(OS)were investigated.Results:107 patients were included,including 63 cases in the combination group and 44 cases in the monotherapy group.The ORR were 78%and 50%(P=0.003),and DCR were 97%and 77%(P=0.002),respectively.At a median follow-up of 13.7 mon,a PFS event occurred in 38.1%and 81.8%of patients in the two groups,with median PFS of18.8 mon and 5.3 mon,respectively(P<0.000,1).Median OS was unreached in the combination group,and 27.8 mon in the monotherapy group(P=0.31).According to the Cox multivariate regression analysis,combination therapy was an independent prognostic factor of PFS.Conclusion:In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations,combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy,which should be the preferred treatment option.

Promoter Methylation of the <i>CADM</i>1 and 4.1<i>B</i>Genes Occurs Independently of the <i>EGFR</i>or the <i>KRAS</i>2 Mutation in Non-Small Cell Lung Cancer

Objective: Targeting mutated EGFR by EGFR-tyrosine kinase inhibitors (EGFR-TKI) is a potent approach to a subset of non-small cell lung cancer (NSCLC). However, the response to EGFR-TKI varies in individual cases even among tumors carrying the same?EGFR?mutation, suggesting the involvement of modifying factors. To characterize possible modifiers, we examined mutation state of the?EGFR?and the?KRAS?genes in Japanese NSCLC and compared them with the methylation state of lung tumor suppressors, the?CADM1 and?4.1B,?whose products have potentials to modify the functions of EGFR or KRAS. Materials and methods: A total of 103 Japanese NSCLC and 11 NSCLC cell lines were examined. Genomic DNA of exons 18–21 of the?EGFR?and exons 1 and 2 of the?KRAS?were amplified by polymerase chain reaction (PCR), followed by single-strand conformation polymorphism analysis and direct sequencing. Methylation status of gene promoters in NSCLC cells were examined by methylation-specific PCR. Results: Mutations of the?EGFR?and?KRAS?were detected mutually exclusively in 27 and 11 out of 103 NSCLC cases, respectively.?EGFR?mutations were observed exclusively in adenocarcinoma (27 of 69, 41%) and preferentially in tumors from female and non-smokers (p < 0.00001). Eight (30%) and 12 (44%) of 27 tumors carrying mutated?EGFR?and 4 (36%) and 8 (73%) of 11 tumors carrying mutated?KRAS?showed methylation of the?CADM1 and 4.1B, respectively.?EGFR-mutated tumors with methylation of either?CADM1 or 4.1B?showed more malignant features than those with unmethylated?CADM1 and 4.1B?(p < 0.05). Conclusion: Methylation state of the?CADM1 and?4.1B?are independent of the mutation status of the?EGFR?or?KRAS?but play roles in the malignant progression of NSCLC. Integration of epigenetic information would be useful for identifying possible modifiers to predict the response or recurrence of lung adenocarcinoma to the EGFR-TKI therapy.

Phase II Study of Carboplatin and Pemetrexed Followed by Gefitinib for Patients with Advanced Non-Small Cell Lung Cancer Harboring Sensitive EGFR Mutation

We conducted a phase II study of combination chemotherapy with carboplatin (Cb) and pemetrexed (Pem) followed by gefitinib (Gef) to determine the effects and toxicities in patients with non-small cell lung cancer (NSCLC) harboring sensitive EGFR mutation. Eligible patients received four courses of Cb at a dose corresponding to a target area under the curve equal to 6 mg/mL·min and 500 mg/m2 Pem on day 1 every three to four weeks followed by sequential Gef 250 mg once a day until tumor progression. Sixteen of registered 28 patients responded to Cb and Pem combination. Twenty-seven patients received sequential Gef and 8 non-responders to Cb and Pem achieved PR. The overall response rate was 85.7%. Among the major toxicities, grade 3 SGPT elevation, nausea and thrombosis were observed in 3, 3 and 1 patients, respectively, who received Cb and Pem, and grade 3 SGPT elevation and dry skin were observed in 5 and 1 patients, respectively, who received Gef. There was no febrile neutropenia and no treatment-related death. The median progression-free survival time was 19.1 months. Among 21 patients who were followed up for more than 2 years, 14 survived during that time. Cb and Pem followed by Gef maintenance are recommended for further evaluation for patients with metastatic NSCLC harboring sensitive EGFR mutation.

The Impact of Chemotherapy on EGFR Mutation Status in Non-Small-Cell Lung Cancer: A Meta-Analysis

Background: Emerging evidence indicates that chemotherapy for lung cancer may alter EGFR mutation status. However, whether chemotherapy as a firstline treatment may increase or reduce the frequency of EGFR mutations in NSCLC remains uncertain. Therefore, we conducted a meta-analysis to evaluate whether chemotherapy leads to altered EGFR mutation status. Methods: A systematic literature search was performed using the PubMed, OVID, Science Direct, Cochrane Library, and CNKI databases for studies on pre- and post-chemotherapy EGFR mutation status. Relevant studies documenting perichemotherapy EGFR mutation ratios were included. Analyses of pooled odds ratios (OR) were performed. Results: Six studies involving 656 patients were included in this meta-analysis. It was found that chemotherapy may alter EGFR status (OR = 1.93, 95% CI 1.05 - 3.56;p < 0.0001). No significant differences in EGFR mutation alterations were observed in terms of gender, smoking history, EGFR loci, or chemotherapy response in NSCLC patients. Conclusions: Chemotherapy may contribute to altered EGFR status. NSCLC patients with EGFR mutations might need to be considered for EGFR status redeterminations prior to second-line EGFR-TKI treatment or upon tumor recurrence after chemotherapy. Further randomized clinical trials should investigate the impact of neoadjuvant or first-line chemotherapy on EGFR mutation status in NSCLC patients.

Gefitinib combined with γ-ray stereotactic body radiation therapy has better efficacy than gefitinib alone for senile lung adenocarcinoma patients with EGFR mutations as first-line regimen

Objective： The senile lung adenocarcinoma patients harboring an activating epidermal growth factor receptor （EGFR） mutation shows good and rapid response to EGFR tyrosine kinase inhibitors （TKIs）. Whether gefitinib combined with y-ray stereotactic body radiation therapy has better efficacy than gefitinib alone for senile lung adenocarcinoma patients with EGFR mutations as first-line regimen is still under investigation. Methods： The 42 senile lung adenocarcinoma patients with EGFR mutations were divided into 2 groups according to the therapy method. Group A was the 22 patients treated with gefitinib combined with y-ray stereotactic body radiation therapy （SBRT）. Group B was the 20 patients treated with gefitinib alone. All of the patients received gefitinib of 250 mg/d from the first day until disease progression or other reasons. The patients of Group A were treated with y-ray stereotactic body radiation therapy from the second day. Radiation fields included the primary lesions and the integration of lymph nodes. Dose curve of this group was 50%-80%. Encircled dose was 4.0-6.5 Gy per fraction and the range of total dose was 40-52 Gy. We treated the patients 8-12 times and treated five times every week. Results： All the patients were examined by enhanced double helix CT at the second month. The tumor response rate （RR） of group A was 81.8% （18/22）. Disease control rate （DCR） was 90.9% （20/22）. The median overall survival （OS） was 24.2 months （range 8-58 months ） and the progression-free survival （PFS） was 18.6 months. The overall 1-year survival rate was 72.3% （16/22） and 2-year survival rate was 54.5% （12/22）. The main side effects included skin rash and diarrhea. The RR of group B was 50.0 % （10/20）. DCR was 75.0% （15/20）. OS was 17.4 months （range 6-32 months ） and PFS was 12.1 months. The overall 1-year survival rate was 60.0% （12/20） and 2-year survival rate was 40.0% （8/20）. The main side effects included skin rash and diarrhea. The group A who were treated with gefitinib combined with y-ray stereotactic body radiation therapy had a higher short term therapeutic effects （RR） and long term therapeutic effects （OS） than group B who were treated with gefitinib alone respectively （81.8% vs 50.0%, P = 0.029 〈 0.05, x2 = 4.773 and 24.2 vs 17.4, P = 0.024 〈 0.05, X2 = 5.098）. Conclu. sion： Gefitinib combined with y-ray stereotactic body radiation therapy has better efficacy than gefitinib alone for senile lung adenocarcinoma patients with EGFR mutations as first-line regimen. The side affects are acceptable.

Analysis of EGFR gene mutations in lung adenocarcinoma in Karamay,Xinjiang,China

Background:To investigate the mutation types and mutation rate of the epidermal growth factor receptor(EGFR)gene in patients with lung adenocarcinoma and the clinical features of lung adenocarcinoma with EGFR gene mutations in Karamay,Xinjiang,China.Methods:Paraffin-embedded tissue samples of adenocarcinoma patients were collected in the Karamay Central Hospital from March 2016 to June 2019,and mutations in exon 18–21 of the EGFR gene were detected by the allele-specific amplification polymerase chain reaction(Amplification RefractoryMutation System–PCR)method.The relationships between themutation types,mutation incidence,and clinical features were analyzed.Results:Of the 170 patients with lung adenocarcinoma,83 had EGFR mutations.The total mutation rate of EGFR in patients with lung adenocarcinoma was 48.8%,which included mutations in exons 18(1.2%[2/170]),19(19.4%[33/170]),20(2.4%[4/170]),and 21(20.6%[35/170]).Intriguingly,there was a case with 9 mutations in exons 20 and 21.The mutations in exon 19 of EGFR resulted in the deletion of codons 746 to 750.The main mutation in exon 21 was L858R(91.4%[32/35]).There was no significant difference in exons 19 and 21 mutation rates(P>0.05).The mutation rate of EGFR in female patients was significantly higher than that in male patients(P<0.05)but had no correlation with the age,smoking status,and clinical stage of patients with non–small cell lung cancer(P>0.05).The EGFR mutation rate may be related to the degree of tumor differentiation.Conclusions:Among patients with lung adenocarcinoma in Kelamayi(city in Xinjiang),EGFR mutations were more frequently detected in female patients,and the main sites of mutations were exons 19 and 21.

Amivantamab联合lazertinib一线治疗EGFR敏感突变晚期NSCLC:评MARIPOSA研究

1文献来源Cho BC,Felip E,Spira AI,et al.Amivantamab plus lazertinib versus osimertinib as first⁃line treatment in patients with EGFR⁃mutated,advanced non⁃small cell lung cancer(NSCLC):primary results from MARIPOSA,a phaseⅢ,global,randomized,controlled trial[J].Ann Oncol,2023,34(2S):S1306.

非小细胞肺癌EGFR基因少见突变P733L对第1代和第3代EGFR-TKI敏感性的研究

目的:探讨表皮生长因子受体(EGFR)基因少见突变P733L对第1代和第3代EGFR酪氨酸激酶抑制剂(EGFR-TKI)的敏感性。方法:通过四唑盐比色法和平板克隆实验分析EGFR L858R和P733L肺癌细胞对第1代和第3代EGFR-TKI的敏感性;通过Transwell实验分析第1代和第3代EGFR-TKI对EGFR L858R和P733L肺癌细胞迁移的抑制作用;通过检测凋亡蛋白分析第1代和第3代EGFR-TKI促进EGFR L858R和P733L肺癌细胞凋亡的作用。结果:第1代和第3代EGFR-TKI对EGFR L858R和P733L细胞的增殖、克隆形成和细胞迁移都有抑制作用。与EGFR野生型肺癌细胞相比,第1代和第3代EGFR-TKI处理后,EGFR L858R和P733L细胞的EGFR激酶活性受到抑制,细胞凋亡明显增加。结论:EGFR P733L突变细胞对第1代和第3代EGFR-TKI的敏感性与EGFR L858R突变细胞的敏感性相似,本研究为EGFR基因少见突变从EGFR-TKI治疗中获益提供了实验证据。