Immunohistochemistry (IHC) with EGFR mutation-specific monoclonal antibodies (mAbs) for screening EGFR mutations in non-small cell lung cancer (NSCLC) patients (p).

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 7570-7570
Author(s):  
S. Simonetti ◽  
M. A. Molina ◽  
C. Mayo ◽  
J. Bertran-Alamillo ◽  
T. Moran ◽  
...  
2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18106-e18106
Author(s):  
Francisco Lobo ◽  
Manuel Domine ◽  
Federico Rojo ◽  
Yann Izarzugaza ◽  
Ana Leon ◽  
...  

e18106 Background: Mutations in the Epidermal Growth Factor Receptor (EGFR) predict a better outcome to EGFR tyrosine kinase inhibitors than platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Previous studies with Caucasian patients have shown a prevalence of EGFR mutation of 10-15%. The aim of this study is to analyze the prevalence of EGFR mutations in squamous-cell NSCLC patients from an area of influence of 500,000 habitants. Methods: Prospective mutation testing in NSCLC patients included in our institution since October 2010 to January 2012 was performed on DNA obtained from available tumor tissue and cytologic samples, using ARMS-scorpion TheraScreen EGFR 29 Mutation Test Kit (Qiagen). Results: From 218 consecutive NSCLC diagnoses, 18 (8.25%) patients showed EGFR mutations: 6 (33.3%) exon 19 deletion, 9 (50%) exon 21 mutations (7 L858R and 2 L861Q) and 3 (16.6%) cases exon 20 insertion. In the EGFR mutated population, 16 (88.88%) patients were diagnosed as adenocarcinoma and 2 (11.11%) as squamous cell carcinoma. The characteristics of these squamous cell cancer patients were: 2 male; 1 non-smoker, 1 former-smoker; 1 stage IV and 1 stage IB at diagnosis; one case exon 20 insertion and one exon 21 mutation (L858R). Conclusions: The EGFR mutation rate in squamous-cell NSCLC patients in our referral area is superior (11.17%) than previously reported, reinforcing the importance of including EGFR mutation testing in squamous-cell NSCLC population for selecting optimal therapy for these patients.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13120-e13120
Author(s):  
Khoa Trong Mai ◽  
Cam Phuong Pham ◽  
LUNG TIEN Nguyen ◽  
Quynh Thi Thuy Vo ◽  
Nguyen TUAN Anh ◽  
...  

e13120 Background: To determine the epidermal growth factor receptor ( EGFR) mutation status in non-small cell lung cancer (NSCLC) patients in Vietnamese population at Bach Mai Hospital, and relation of different variables to the frequency of EGFR mutations. Methods: The EGFR mutation status of 1451 tissue samples in NSCLC patients and correlation among different variables of age, gender, smoking habit and histology groups were evaluated. Results: A total of EGFR mutation analysis was performed, with an overall mutation rate of 40.7%. The most prevalent categories were in-frame deletions in exon 19 (57.2% of the overall mutations); followed by L858R and L861Q in exon 21 (35.7%); exon 18 (4,6%); double mutation: 2.9%; The T790M mutation in exon 20 represented approximately 2.5%; The pooled prevalence of EGFR mutation was higher in female (60.6%), non-smokers (61.1%), and patients with adenocarcinoma (42.2%). Conclusions: The prevalence of EGFR mutations of NSCLC in Vietnam is higher than that in the West, but comparably equal to that in some Asian countries. It is associated with female sex, non-smoker status, and adenocarcinoma, sample tissue type and age, but not depends on disease stage and tumor sampling.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7176-7176 ◽  
Author(s):  
H. Sakai ◽  
K. Akagi ◽  
J. Sudoh ◽  
S. Yoneda ◽  
H. Komagata ◽  
...  

7176 Background: Recent studies have suggested that EGFR mutations can be used to predict tumor sensitivity to gefitinib (epidermal growth factor receptor tyrosine kinase inhibitor) in patients with non-small-cell lung cancer (NSCLC). Most previous studies of EGFR mutations have used direct sequencing to analyze surgically resected specimens. More rapid, accurate, and simple techniques for analysis of EGFR mutations in histologic or cytologic specimens (i.e., transbronchial biopsy, bronchial washing, pleural effusion, lymph node aspiration) are needed to improve outcomes. Methods: DNA was extracted from histologic or cytologic specimens of NSCLC obtained from March through October 2005. The major mutations of the EGFR gene (exons 18–21) were analyzed by our original technique for fragment analysis and polymerase-chain-reaction-restriction-fragment-length polymorphism analysis. Results: About 2 days were required for mutation analysis. Pathological analysis indicated that 64 (5 histologic and 59 cytologic specimens) of 90 specimens (11 histologic and 79 cytologic specimens) were adenocarcinomas. EGFR mutations were found in 22 of these specimens (2 histologic and 20 cytologic specimens; ex19:del 13, ex19:ins 2, ex21:L858R 7). An EGFR mutation (ex19:del) was also found in a patient with large cell carcinoma. Conclusions: Our method can efficiently detect EGFR mutations in small samples of lung cancer cells obtained from histologic or cytologic specimens. This method is useful for the identification of EGFR mutations in patients with unresectable NSCLC in whom sufficient tissue specimens are difficult to obtain. No significant financial relationships to disclose.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20636-e20636
Author(s):  
Wen-Feng Li ◽  
Jin Kang ◽  
Xu-Chao Zhang ◽  
Su Jian ◽  
Huajun Chen ◽  
...  

e20636 Background: Activation of MET oncogene as the result of amplification or activation MET exon 14 mutations represents an emerging molecular target for non-small cell lung cancer (NSCLC) treatment. MET exon 14 mutations account for 1.0% in Chinese NSCLC patients. However, few data have been reported on the coexisting of MET exon 14 mutations and EGFR mutations in NSCLC. Moreover, the clinicopathological characteristics and targeted therapy of these MET/ EGFR-coexisting patients remain elusive. Methods: Next-generation sequencing was performed on the DNA of 969 patients and Sanger sequencing was conducted on cDNA of 621 patients for MET exon 14 mutations in NSCLCs. EGFR mutations were determined by direct DNA sequencing. Results: Fifteen patients harbored positive MET exon 14 mutations. Frequency of concomitant EGFR and MET exon 14 mutations was 0.2%(3/1590). 3 patients with concomitant MET exon 14 mutation and EGFR activating mutation were all female, never smokers and adenocarcinoma. Their stagings were stageⅠB (n = 1) and stage Ⅳ(n = 2). The stage ⅠB patient harboring concomitant MET exon 14 skipping and EGFR L858R mutation did not relapse 2 years after operation. The other two stage Ⅳ patients received first-line gefitinib. Case one harbored concomitant MET exon 14 point mutations (IVS13-36G > A) and EGFR exon 19 deletion, and showed resistance to gefitinib with progression free survival(PFS) of 2 weeks and overall survival(OS) of 1 month. Case two had concomitant MET exon 14 point mutations (IVS13-36G > A) and EGFR L858R mutation. Meanwhile, she also had both METamplification and c-Met overexpression at the baseline. She showed partial response (PR) to gefitinib with 3.8 months PFS. Then she was enrolled in a clinical trial (NCT02374645) to receive volitinib plus gefitinib on December 20, 2016. Initial response was good PR on January 24, 2017. Only grade 1 rash was observed. Conclusions: Coexisting MET exon 14 /EGFR mutation is an uncommon molecular event in NSCLC patients. Such coexisted patients might show relative resistance to EGFR inhibitor. However, combination of MET and EGFR inhibitors will be potentially a good strategy to overcome such a relative resistance for MET exon 14 /EGFR co-mutant patients.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21691-e21691
Author(s):  
Shaorong Yu ◽  
Ran Hu ◽  
Meiqi Shi

e21691 Background: Anti-PD-1/PD-L1 antibody has been approved as first- or second-line therapy in non-small cell lung cancer (NSCLC) patients and modified the management of patients with locally advanced or metastatic NSCLC. However, anti-PD-1 treatment shows less effective in patients with EGFR mutation than in those without driver gene mutation. To determine the activity of anti-PD-1 antibody in EGFR mutant NSCLC, we retrospectively evaluated response patterns among EGFR mutant NSCLC patients. Methods: We identified 58 patients with EGFR mutation who were treated with anti-PD-1 monotherapy or anti-PD-1 antibody combined with chemotherapy from March 2018 to December 2019. All of patients have received more than one treatment regimen including EGFR-TKI treatment. Objective response rates (ORR) were assessed using RECIST v1.1. Results: A total of 58 patients including 53 cases of lung adenocarcinoma, 4 cases of squamous cell carcinoma and 1 case of adenosquamous carcinoma were analyzed. Among them 26 patients received nivolumab treatment, 9 patients with pembrolizumab treatment, 9 patients with sintilimab treatment, 8 patients with JS001 treatment and 6 patients with camrelizumab treatment. Seven patients received anti-PD-1 monotherapy and the other 51 patients received anti-PD-1 combined chemotherapy. The main chemotherapeutic drugs contain docetaxel, pemetrexed, paclitaxel and paclitaxel-albumin. ORR was observed in 6 out of 58 (10%) patients. The disease control rate was 50% (29/58). The median PFS was 2.82 months. All six patients who achieved PR were received anti-PD-1 combined chemotherapy. Four patients died during treatment with anti-PD-1 therapy and we can’t confirm if these were due to cancer progress or immune related tumor hyperprogression. The adverse events were immune related pneumonia (two cases with grade 2 and one case with grade 3) and immune related hepatitis (one case with grade 2). Conclusions: Anti-PD-1 antibody combined chemotherapy seems showed moderate effect on NSCLC patients with EGFR mutation who have received anti-EGFR therapy.


2010 ◽  
Vol 28 (18) ◽  
pp. 3076-3083 ◽  
Author(s):  
Lecia V. Sequist ◽  
Benjamin Besse ◽  
Thomas J. Lynch ◽  
Vincent A. Miller ◽  
Kwok K. Wong ◽  
...  

PurposeEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have had a significant impact on non–small-cell lung cancer (NSCLC) outcomes, particularly for patients with EGFR mutations. Resistance emerges after 9 to 12 months, primarily mediated by the T790M resistance mutation. We studied neratinib, an irreversible pan-ErbB TKI that may overcome T790M.Patients and MethodsPatients with advanced NSCLC underwent EGFR sequencing of available tumor tissue at enrollment. Those with ≥ 12 weeks of prior TKI therapy were placed in arm A if they were EGFR mutation positive or arm B if they were wild-type. Arm C included TKI-naïve patients with adenocarcinoma and light smoking histories (≤ 20 pack-years). All patients received daily oral neratinib, initially at 320 mg but subsequently reduced to 240 mg because of excessive diarrhea. The primary end point was objective response rate (RR).ResultsOne-hundred sixty-seven patients were treated: 91 in arm A, 48 in arm B, and 28 in arm C. Diarrhea was the most common toxicity; grade 3 incidence was 50% at 320 mg but improved to 25% after dose reduction. The RR was 3% in arm A and zero in arms B and C. No patients with known T790M responded. Notably, three of four patients with an exon 18 G719X EGFR mutation had a partial response and the fourth had stable disease lasting 40 weeks.ConclusionNeratinib had low activity in patients with prior benefit from TKIs and in TKI-naïve patients, potentially because of insufficient bioavailability from diarrhea-imposed dose limitation. Responses were seen in patients with the rare G719X EGFR mutation, highlighting the importance of obtaining comprehensive genetic information on trials of targeted agents.


2014 ◽  
Vol 29 (2) ◽  
pp. 112-119 ◽  
Author(s):  
Rui-chao Li ◽  
Li-jun Zheng ◽  
Ming-hao Fang ◽  
Shi-ying Yu

Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. The upregulation of the epidermal growth factor receptor (EGFR) due to mutations has been observed in a number of cancers, and tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, which specifically target EGFR signaling, have been used to treat NSCLC patients. The presence of EGFR mutations was previously shown to confer sensitivity to TKIs. In this study, we evaluated the correlation between EGFR mutations and response to erlotinib in Chinese NSCLC patients. We recruited 36 patients with stage IIIB/IV NSCLC who had failed first-line chemotherapy, and treated them with erlotinib. We used immunohistochemistry to determine EGFR expression, and we screened for mutations using PCR analysis. We used Cox regression analysis and Kaplan-Meier curves for survival analysis. We found that 8 patients had exon 19 mutations, while 3 patients had exon 21 mutations. An Eastern Cooperative Oncology Group (ECOG) grade of 2 was a significant negative predictor of overall survival (OS). Patients with EGFR mutations showed a significantly better OS compared to those without EGFR mutations. Additionally, multivariate analysis showed that erlotinib-treated stage IV patients had a significantly longer progression-free survival (PFS) compared to stage IIIB patients. Patients with EGFR mutations also had a significantly better PFS compared to those without EGFR mutations. The overall remission rate (22.2%) and disease control rate (75%) were significantly higher compared to the rates after second-line chemotherapy (<10%). In conclusion, the presence of EGFR mutations could be a marker to predict the therapeutic efficacy of erlotinib and the prognosis in Chinese NSCLC patients.


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