Exploring the applicability of immunotherapy in different EGFR mutation subgroups based on data analysis of 9,659 Chinese patients with NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21020-e21020
Author(s):  
Hao Peng ◽  
Hushan Zhang ◽  
Libin Zhang ◽  
Yang Wang ◽  
Xudong Shen ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Egfr Mutation ◽  
Clinical Laboratory ◽  
Checkpoint Inhibitors ◽  
White Blood Cells ◽  
Chinese Patients ◽  
Egfr Mutations ◽  
Wild Type ◽  
Tissue Samples ◽  
Nsclc Patients

e21020 Background: Here we assessed TMB level, PD-L1 expression, and their correlation in 9649 Chinese NSCLC patients with or without EGFR mutation, and different subtypes of EGFR mutations, to find out the underlying mechanisms that different outcomes of ICI for EGFR wild type and EGFR mutation NSCLC patients, and the possibility of ICI therapy for NSCLC patients of different EGFR mutation subtypes. Methods: Tumor tissue samples of 9649 NSCLC patients were collected from Janary 2018, expression of PD-L1 were detected by using Dako PD-L1 IHC 22C3 pharmDx, Tumor Proportion Score (TPS) was used to determine expression of PD-L1. Gene mutation was detected by means of next generation sequencing (NGS). Performed Whole-Exome Sequencing (WES) on 70 tissue samples and corresponding White Blood Cells (WBCs) as matched control. Other samples were detected with panel covering whole exon regions of 733 cancer related genes. All these detections were performed in a College of American Pathologists (CAP)-certified and Clinical Laboratory Improvement Amendments (CLIA)-accredited lab for gene mutation analysis (3D Medicines Inc.,Shanghai, China). Statistical analysis was performed using GraphPad Prism (version 7.01) and SPSS version 21.0 (SPSS,Inc.). Results: Results showed that the proportion of EGFR mutation in Chinese patients with NSCLC was 51.3%, and the proportion of EGFR mutation subtypes were 42.6% L858R, 39.5% exon 19del, 2.3% exon 20in, 4.3% T790M. These samples were divided into different groups according to EGFR mutation, both WES based and panel-based results showed that EGFR wild type group displayed higher TMB level than EGFR mutation group (P < 0.05). However, except for exon 19del, L858R, exon 20in, no significant differences were found between wild type and other EGFR mutation subtypes. Furthermore, results of IHC revealed that, higher proportion of strong positive PD-L1 expression (TPS≥50) were found in EGFR wild type than exon 19del, L858R and exon 20in, no significant correlation was found between TMB level and PD-L1 expression. Conclusions: EGFR mutations account for half of Chinese NSCLC patients. The biomarkers of immune checkpoint inhibitors (such as TMB and PD-L1) are different in various EGFR mutation subtypes, which may indicate that for some NSCLC patients with EGFR mutation subtypes, they may also respond to ICI treatment as wild-type.

EGFR mutations and the correlation with gefitinib therapy in Chinese NSCLC—A systematic review based on individual patient data from 5 medical centers in China

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7187-7187 ◽  
Author(s):  
Y. Wu ◽  
W. Zhong ◽  
L. Li ◽  
L. Zhang ◽  
C. Zhou ◽  
...  
Keyword(s):  
Mutation Rate ◽  
Egfr Mutation ◽  
Meta Analysis ◽  
Univariate Analysis ◽  
Correlation Factor ◽  
Chinese Patients ◽  
Egfr Mutations ◽  
Medical Centers ◽  
Nsclc Patients ◽  
Wild Group

7187 Background: EGFR mutations were found to have a significant association with response to gefitinib. To date, information on status of EGFR mutation in Chinese remains scanty. Comprehensive review of existing information on EGFR mutations is essential for treatment selection in Chinese patients with advanced NSCLC. Methods: We published 4 abstracts on EGFR mutation in Chinese patients at the 41st ASCO. We performed an IPD-meta-analysis on the data from the above investigators plus another one. The original individual EGFR mutations (exon 18,19,21) data was collected. Gefitinib was given with 250 mg/d until disease progression. Results: Total 407 cases were into the IPD review. The patient characteristic was male: female = 258:149; adenocarcinoma: other = 259:148; smoker: nonsmoker =178:153. The EGFR mutation rate was 3.05% (124/407). For adeno subgroup the EGFR mutation rate was 42.5% (110/259), non- adeno was 9.5% (14/148). In female the EGFR mutation rate was 41.6% (62/149), male was 24.0% (62/258). Non-smoker was 39.2% (60/153), smoker was 18.5% (33/178). In univariate analysis adeno, smoking, gender was significant predictive factors for EGFR mutation but in logistic regression only adeno is independent correlation factor (p = 0.000, 95% CI 2.078—9.001). Conclusions: The EGFR mutation is more common in no-smoking female adeno patients with NSCLC. The EGFR mutation group has a tendency of response rate to gefitinib compare to the EGFR wild group in NSCLC patients. [Table: see text] No significant financial relationships to disclose.

Association of plasma EGFR mutations with response to first-line chemotherapy and prognosis in Chinese patients with advanced non-small cell lung cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19017-e19017
Author(s):  
M. N. Wu ◽  
J. Zhao ◽  
H. Bai ◽  
M. L. Zhuo ◽  
S. H. Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stage Iv ◽  
Small Cell ◽  
Chinese Patients ◽  
Egfr Mutations ◽  
Wild Type ◽  
Small Cell Lung ◽  
First Line ◽  
Nsclc Patients ◽  
Line Chemotherapy

e19017 Background: To investigate associations of plasma EGFR mutations of advanced non-small cell lung cancer (NSCLC) patients with response to the first-line chemotherapy and prognosis. Methods: Plasma EGFR mutations from 145 chemotherapy-naive patients with advanced or metastatic NSCLC were examined by using denaturing high- performance liquid chromatography (DHPLC), and associations of EGFR mutations with tumor response to chemotherapy and clinical outcomes were evaluated. Results: 37.2% (54/145) of the patients was detected to have EGFR mutations in their plasma DNA. The response rate of mutated EGFR carriers to the chemotherapy was 37% (20/54), similar to that of 31.9% (29/91) of wild-type EGFR carriers to the chemotherapy (P= 0.323). Stage IV NSCLC patients with mutated EGFR had a longer PFS than those with wild-type EGFR (4 vs 3 months, P=0.043) after the first-line chemotherapy. The median survival time and 1-, 2- year survival rate for the patients with EGFR mutations (24 months and 85.7%,43.7%) were increased than those with wild-type EGFR (18 months and 65.7%,25.9%) (p=0.0468). Cox multivariate regression analysis showed that clinical stage (IV vs IIIb), response to the first-line chemotherapy (PR vs PD), and EGFR mutations were independent prognostic factors (P=0.008, 0.000 and 0.000 respectively). Conclusions: We conclude that plasma EGFR mutations in the Chinese patients with advanced NSCLC were not associated with response to the first-line chemotherapy, but Stage IV NSCLC patients with mutated EGFR had a longer PFS after the chemotherapy. No significant financial relationships to disclose.

Phase II study of gefitinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) gene mutations detected by PNA-LNA PCR clamp

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7076-7076 ◽  
Author(s):  
A. Sutani ◽  
Y. Nagai ◽  
K. Udagawa ◽  
Y. Uchida ◽  
Y. Murayama ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Response Rate ◽  
Phase Ii Study ◽  
Gene Mutations ◽  
Egfr Mutations ◽  
Wild Type ◽  
First Line ◽  
Egfr Gene ◽  
Nsclc Patients ◽  
Egfr Genes

7076 Background: The responsiveness to gefitinib has been reported to closely link to the presence of EGFR gene mutations. We developed a method, PNA-LNA PCR clamp, capable of detecting EGFR mutations in the presence of 100-fold background of wild type EGFR from normal cells (Can Res. 2005;65:7276). This study was prospectively designed to evaluate 1) the sensitivity and the specificity of the PNA-LNA PCR clamp (sample size > 100 pts) and 2) a phase II study of gefitinib for NSCLC patients (pts) with EGFR gene mutations (sample size > 25 pts to show the lower limit of 95% CI > 50%). Methods: Clinical samples (sputum, pleural effusion, bronchial fluid and paraffin tissue) were obtained from consecutive NSCLC pts with informed consent in our institution, and were tested by the PNA-LNA PCR clamp. After the second informed consent, for PS 0–2, inoperable stage III and IV pts with EGFR mutations, gefitinib (250mg P.O. daily) was given as the second treatment after docetaxel containing chemotherapy. In case of poor PS pts, the first line chemotherapy was omitted. Results: From Sept. ’04 to Oct. ’05, samples from 100 of a total of 107 pts were informative of EGFR mutation status. PNA-LNA PCR clamp detected EGFR mutations in 38 pts (38%) (15 males/23 females; median age:62; adenoca.:33 pts). Exon 19 deletions, L858R and L861Q were found in 25 (66%), 12 (32%) and 1 (2%) patients, respectively. But 62 pts (51 males/11 females; median age:66; Ad:43 pts) were judged to have wild type EGFR. Between positive and negative pts in EGFR mutation, there was significant difference in the distinction of sex (p = 0.00001). Gefitinib was given to 26 pts with EGFR mutations as the first line (4 pts) or the second line treatment (22 pts). One patient and 20 patients showed CR and PRs, respectively, and the response rate was 81% (95% CI: 61–94%). For patients with wild EGFR genes, gefitinib was given to 5 patients and one patient (20%) showed PR. The response rate was significantly different between wild and mutant EGFR genes detected by the PNA-LNA PCR clamp (p = 0.017). Conclusions: PNA-LNA PCR clamp could reliably detect EGFR mutations, indicating the method is useful to detect EGFR mutations in clinical specimens. Updated data will be presented at the meeting. No significant financial relationships to disclose.

scholarly journals Outcomes of 27 Non-Small Cell Lung Cancer Patients Receiving Resections of Paired Primary Pulmonary and Brain Metastatic Tumours: Is EGFR Negative Mutation of Brain Metastasis Bring More Benefit?

2021 ◽  
Author(s):  
Shuonan Xu ◽  
Jianfei Zhu ◽  
Daixing Zhong ◽  
Yanmin Xia ◽  
Yingsheng Wen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Egfr Mutation ◽  
Egfr Mutations ◽  
Lung Tumour ◽  
Wild Type ◽  
Small Cell Lung ◽  
Mutant Type ◽  
Paired Tumour ◽  
Nsclc Patients ◽  
Primary Lung Tumour

Abstract Background: To analyze the heterogeneity and clinical outcomes of epidermal growth factor receptor (EGFR) gene mutation in primary tumour and corresponding brain metastasis(BM) in non-small cell lung cancer (NSCLC).Methods: Primary pulmonary tumours and paired metastatic brain tumours were surgically removed from twenty-seven NSCLC patients from July 1999 to November 2013 in our hospital. All brain lesions were confirmed as metastases stemming from NSCLC by pathological examination. EGFR gene (exons 18-21) mutant status was detected in matched tumour by using amplification refraction mutation system (ARMS). If inconsistency was detected, the paired tumour was evaluated again. The McNemar test was performed to compare the consistency of the paired tumour, and the Kappa test was used to quantify the agreement of both methods.Progression free survival(PFS) and overall survival(OS) were exhibited by the Kaplan-Meier.Results: In this study, of the 27 patients, nine (33.3%) cases were found to have EGFR mutations in BMs, and ten (37.0%) patients were detected positive EGFR status in primary lung tumour tissue. The rate of consistency of the matched tumour was 24/27 (88.9%, P≤0.001), and the Kappa coefficient was 0.757. Among the three cases presenting EGFR mutational heterogeneity, two patients harbored EGFR mutation in primary tumors but was negative in BMs, meanwhile, the other patient had the opposite pattern. Comparing to patients with consistent EGFR mutations(both mutant or wild),patients with inconsistent EGFR mutations tended to have better outcomes, including PFS(37.2months vs 25.0months vs 16.5months,P=0.159) and OS(53.6months vs 27.5months vs 26.8months,P=0.380), further analysis showed that two patients whose EGFR mutant-type primary tumor progressing to wild-type cerebral metastastic tumor might have longer overall survival(53.6months,37.8months) than one patient harboring reverse mutant difference(EGFR wild-type primary tumor progressing to mutant-type brain metastastic tumor) (16.7months). Also we found that patients with wild type in brain metastatic tumour had longer overall survival (OS)(mOS, 36.3 months vs 29.1months, P = 0.944).Conclusions: EGFR mutation status in NSCLC patients between primary lung tumour and paired BM was heterogeneous, patients harbored wild type EGFR mutation in BM might have better outcomes, especially for positive status transferred to wild.

A novel mutant-enriched liquidchip for detection of circulating EGFR mutations in advanced non-small cell lung cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14526-e14526
Author(s):  
S. Lu ◽  
H. Yang ◽  
X. Ye ◽  
X. Xu ◽  
Z. Li ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Direct Sequencing ◽  
Small Cell ◽  
Egfr Mutations ◽  
Wild Type ◽  
Small Cell Lung ◽  
Exon 19 Deletion ◽  
L858r Mutation ◽  
Nsclc Patients ◽  
Exon 19

e14526 Background: We developed a novel technology, Mutant-enriched liquidchip (MEL), which integrates the sensitive mutant enriched PCR and quantitative high throughput liquidchip (suspension array), to detect circulating EGFR mutations (Exon 19 deletion and exon 21 L858R mutation) in patients with advanced non-small cell lung cancer (NSCLC). Methods: To enrich mutant EGFR, a unique restriction site is introduced into the mutation alleles so that the wild type sequence can be selectively removed by restriction digestion, and the undigested mutated DNA is amplified by PCR. The product is then hybridized to complementary probes (including 15 types of exon 19 deletion and exon 21 L858R mutation) which had been conjugated to beads coding with different fluorescent dye, followed by measuring through Luminex 200 system. Plasmid DNA mixture with different EGFR genotypes was applied to determine the sensitivity and accuracy of MEL. Afterwards, the MEL was validated in 49 patients whose EGFR genotypes of tissue specimen had been tested with direct sequencing The circulating genomic DNA was obtained from serum sample of other 201 Chinese stage IIIB or IV NSCLC patients without EGFR-TKI administration, and the EGFR mutation status was analyzed by using of MEL. Results: The results shows that MEL is capable of detecting as few as 20 copies of mutant EGFR alleles with a sensitivity limit of at least mutant/wild-type ratio of 0.1%. It also shows that MEL can not only confirm EGFR mutations status in tissue specimens already known by direct sequencing (13/49), but also detect mutations in some of those showing wild type by sequencing (16/49). Overall, 54% of patients had circulating EGFR mutation. 34% of patients had an exon 19 deletion and 29.6% had L858R. 63.1% of mutations were found in females and 67.6% in never-smokers. Conclusions: This novel MEL method allows for highly sensitive and reproducible detection of human somatic mutations in heterogeneous specimens, and could be applicable to test EGFR mutations non-invasively in advanced NSCLC patients for predicting response to targeted therapy. No significant financial relationships to disclose.

KRAS and EGFR status as predictive markers of response and time to progression in EGFR wild-type stage IV non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine-kinase inhibitors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19000-e19000
Author(s):  
Manuel Domine ◽  
Federico Rojo ◽  
Tatiana Hernandez ◽  
Sandra Zazo ◽  
Gloria Serrano ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Copy Number ◽  
Egfr Mutation ◽  
Egfr Mutations ◽  
Wild Type ◽  
Time To Progression ◽  
Egfr Amplification ◽  
Combined Analysis ◽  
Nsclc Patients ◽  
Egfr Tki

e19000 Background: KRAS mutations on codons 12, 13 and 61 result in the constitutive activation of protein, which may render tumor cells independent of epidermal growth factor receptor (EGFR) signalling and thereby resistant to tyrosine-kinase inhibitor (TKI) therapy in NSCLC patients. This study was aimed to evaluate the associations of KRAS and EGFR copy number alteration and mutations with response and time to progression (TTP) in EGFR TKI-treated patients. Methods: 84 samples from NSCLS patients treated with erlotinib or gefitinib were analyzed for KRAS and EGFR mutation status by cobas KRAS and EGFR Mutation Tests (Roche). EGFR copy number was determined by fluorescent in situ hybridization (FISH, Abbott Molecular) and amplification was defined with three or more gene copies in tumor. Results: KRAS mutation was detected in 15 (17.8%) cases, EGFR mutation in 27 (32.1%) and EGFR amplification in 8 (9.5%). Significant differences were detected in response rates for wild-type (0.2) and mutant KRAS (0.0) (p=0.023), for wild-type (0.12) and mutant EGFR (0.39) (p=0.007), and for non-amplified (0.18) and EGFR-amplified (0.71) patients (p=0.005). Additionally, significant benefit from TKI therapy was observed for KRAS wild-type compared with KRAS-mutated patients (median TTP 7 vs. 3 months, p=0.001), for EGFR-mutated compared with wild-type patients (14 vs. 4 months, p=0.004) and for EGFR-amplification in contrast to non-amplified cases (11 vs. 5 months, p=0.001). KRAS and EGFR mutations or EGFR amplification did not correlated with overall survival (18 vs. 19 months, p=0.406; 16 vs. 21 p=0.094; 25 vs. 17 months, p=0.103, respectively). Combined analysis of favourable status of three biomarkers strongly predicted benefit to TKI therapy (median TTP 15 vs. 3 months, p<0.001). Conclusions: Combined analysis ofKRAS mutation, EGFR mutation and EGFR amplification in EGFR TKI-treated NSCLC might provide superior predictive information than single biomarker study in these patients.

Evaluation of different MET genotypes as biomarkers for immunotherapy outcomes in NSCLC patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21032-e21032
Author(s):  
Xuanzong Li ◽  
Linlin Wang
Keyword(s):  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Rank Test ◽  
Wild Type ◽  
Exact Test ◽  
Entire Cohort ◽  
Kaplan Meier ◽  
Tumor Mutational Burden ◽  
The Difference ◽  
Nsclc Patients

e21032 Background: Previous studies suggested that MET exon 14 ( METex14) mutation regarding as a distinct subset was sensitive to MET-inhibitors, but poorly response to immunotherapy. Conversly, MET non-exon-14 (non-ex14) mutations including those undetermined functions and affecting the kinase or extracellular domains were found to be associated with the resistance to MET-inhibitors. However, therapeutic strategies for MET-non-ex14 mutant cancer are still largely unknown, and the relationship between MET-non-ex14 mutations and the efficacy of immune checkpoint inhibitors (ICIs) has never been reported. Using two public ICIs-treated cohorts, we aimed to assess the role of MET mutations including both METex14 and MET-non-ex14 mutations in NSCLC patients undergoing ICIs therapy. Methods: A total of 385 ICIs-treated NSCLC patients were enrolled to our study. MET mutations were defined as any nonsynonymous mutations, and we divided them into METex14 and MET-non-ex14 mutation subsets according to the mutated-position on MET. Kruskal-Wallis test was used to analyze the difference of tumor mutational burden (TMB) score, and the Fisher’s exact test was applied to compare the rates of durable clinical benefit (DCB). Log-rank test was used to analyze the differences between Kaplan-Meier survival curves. Results: In the entire cohort, we found that 17 patients (17/385, 4.4%) had MET mutations, most of which were pure METex14 mutations (10/17, 58.8%). The median TMB of patients in the entire NSCLC cohort was 6.89 mut/Mb. MET-non-ex14 mutant patients (7/385, 1.8%) possessed a significantly higher TMB than METex14-mutant (10/385, 2.6%) and MET wild-type (368/385, 95.6%) sub-cohorts, respectively (median TMB, 17.92 mut/Mb versus 4.17 mut/Mb, p = 0.008; 17.92 mut/Mb versus 6.96 mut/Mb, p = 0.01, respectively). DCB was more common in patients harbored MET-non-ex14 mutations than patients with METex14 mutations and MET wild-type (66.7% versus 14.3%, p = 0.103; 66.7% versus 29.9%, p = 0.075, respectively). We found that patients with MET-non-ex14 mutations had a numerically longer progression free survival (PFS) than those with METex14 mutations and MET wild-type (p = 0.169). Moreover, the PFS was significantly longer in MET-non-ex14-mutant subgroup than patients with METex14 mutations (median PFS, 9.1 versus 2.1 months, p = 0.025). Correspondingly, the overall survival (OS) was significantly longer in MET-non-ex14-mutant subgroup than their wild-type counterparts (median OS, not reached versus 11 months, p = 0.039). Additionally, patients with MET-non-ex14 mutations exhibited relatively better OS versus METex14-mutant patients (median OS, not reached versus 18 months, p = 0.175). Conclusions: MET-non-ex14 mutations were associated with higher TMB, improved DCB rate, and could act as a favorable prognostic biomarker in ICIs-treated NSCLC patients.

Differential responses to therapy in Hispanic NSCLC patients with EGFR, KRAS, or TP53 mutations.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21027-e21027
Author(s):  
Fahmin Basher ◽  
Diana Saravia ◽  
Gilberto Lopes
Keyword(s):  
Checkpoint Inhibitors ◽  
Egfr Mutations ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Kras Mutations ◽  
Tp53 Mutations ◽  
Hispanic Patients ◽  
Tumor Mutational Burden ◽  
Receive Treatment ◽  
Nsclc Patients

e21027 Background: Hispanic (H) patients with non-small cell lung cancer (NSCLC) tend to have more advanced disease at time of diagnosis and less likely to receive treatment compared to non-Hispanic white (NHW) Americans. While survival outcomes do not differ greatly, Hispanic patients tend to have lower response rates to immunotherapy and to targeted therapy with known EGFR mutations. We sought to determine if Hispanic patients with other common mutations present in NSCLC also demonstrate suboptimal responses to therapy compared to NHW patients. Methods: We performed a retrospective review of 468 patients with advanced stage NSCLC at the University of Miami / Sylvester Comprehensive Cancer Center who underwent next-generation sequencing (NGS) for whom treatment outcomes could be identified. Genomic results were obtained from Guardant360 and Foundation One testing in blood or tissue, respectively. Results: In our cohort, 154 patients (33%) were of Hispanic ethnicity, while 279 patients (60%) were NHW. Median age at time of diagnosis was 59, and 50% were male. PD-L1 status was known for 217 patients, with 110 expressing some level of PD-L1. EGFR mutations were present in 25% of all patients, KRAS mutations in 25%, and TP53 mutations in 61%. Average tumor mutational burden was 4.0 in Hispanic patients and 3.6 in NHW patients. We compared outcomes in patients receiving any therapy as well as those specifically receiving immune checkpoint inhibitors (ICI). No differences in OS were observed in our overall patient cohort between H and NHW patients. However, when stratifying patients with EGFR or KRAS mutations, Hispanic patients exhibit significantly shorter OS than their NHW counterparts. In patients with TP53 mutations, we observed no differences between H and NHW outcomes considering all therapy, but Hispanic patients exhibited improved OS with the use of ICI. Conclusions: Our data suggest that the presence of certain mutations in Hispanic patients with advanced NSCLC may serve some prognostic value in predicting responses to therapy, specifically the use of ICI. Further investigation is indicated to determine mechanisms leading to inferior responses after ICI therapy in Hispanic patients.[Table: see text]

Investigation of immune microenvironment in EGFR mutant NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20517-e20517
Author(s):  
Yi Hu ◽  
Longgang Cui ◽  
Xiaochen Zhao ◽  
Yuezong Bai ◽  
Fan Zhang
Keyword(s):  
T Cells ◽  
Egfr Mutation ◽  
Tumor Stroma ◽  
Median Number ◽  
Egfr Mutations ◽  
Wild Type ◽  
Immune Microenvironment ◽  
Regulatory Pathways ◽  
Significant Difference ◽  
Egfr Mutant

e20517 Background: Immune checkpoint inhibitor therapy has made great achievements in NSCLC, but patients with EGFR mutations have poor efficacy with immunotherapy. Previous studies have explored the expression of PD-L1, neo-antigen, co-mutation and regulatory pathways in EGFR mutate NSCLC. This work compared the immune microenvironment of EGFR mutant and wild-type NSCLC. Methods: Patients: NSCLC. Using multi-color immunohistochemistry (multi-IHC) to evaluate the expression of 2 indicators in tumors and tumor stroma, namely CD8+ T cell and macrophage. Shapiro-Wilk was used for normality test, and t-test or Mann-Whitney U test was used according to the results. Two-sided P < 0.05 was considered a significant difference. Results: The study included 119 NSCLC patients, including 59 women (49.6%) and 60 men (50.4%), with a median age of 57. There were 68 patients (57.1%) with EGFR mutations, 19 patients (16%) with KRAS mutations, and 58 patients (48.7%) with TP53 mutations. multi-IHC results showed that, EGFR mutation Vs EGFR wild type samples, (1) the number and proportion of CD8+ T cells in tumor were not statistically different. The median number of CD8+ T cells in tumor stroma was 231.5 vs 359, p = 0.05 and the proportion of CD8+ T cells was 3.92% vs 5.64%, p = 0.02; (2) The median number of macrophage in tumors was 1522 vs 110, p < 0.01, and the proportion of macrophage cells was 24.93% Vs 1.38%, p < 0.01. The median value of macrophages in tumor stroma was 617.5 Vs 208, p < 0.01, and the proportion of macrophages cells was 10.88% vs 3.03%, p < 0.01. Conclusions: Compared with EGFR wild-type patients, EGFR mutation patients have a lower proportion of CD8+ T cells and a higher proportion of macrophages in the immune microenvironment.

scholarly journals Targeted Assessment of the EGFR Status as Reflex Testing in Treatment-Naive Non-Squamous Cell Lung Carcinoma Patients: A Single Laboratory Experience (LPCE, Nice, France)

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 955 ◽  
Author(s):  
Sandra Lassalle ◽  
Véronique Hofman ◽  
Simon Heeke ◽  
Jonathan Benzaquen ◽  
Elodie Long ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Egfr Mutation ◽  
Egfr Mutations ◽  
Wild Type ◽  
Pcr Assay ◽  
Cell Lung Carcinoma ◽  
Specific Pcr ◽  
Treatment Naïve ◽  
Reflex Testing ◽  
Single Laboratory

Background: Assessment of actionable EGFR mutations is mandatory for treatment-naïve advanced or metastatic non-squamous lung carcinoma (NSLC), but the results need to be obtained in less than 10 working days. For rapid EGFR testing, an EGFR-specific polymerase chain reaction (PCR) assay is an alternative and simple approach compared to next generation sequencing (NGS). Here, we describe how a rapid EGFR-specific PCR assay can be implemented in a single laboratory center (LPCE, Nice, France) as reflex testing in treatment-naïve NSLC. Methods: A total of 901 biopsies from NSLC with more than 10% of tumor cells were prospectively and consecutively evaluated for EGFR mutation status between November 2017 and December 2019 using the Idylla system (Biocartis NV, Mechelen, Belgium). NGS was performed for nonsmokers with NSLC wild type for EGFR, ALK, ROS1, and BRAF and with less than 50% PD-L1 positive cells using the Hotspot panel (Thermo Fisher Scientific, Waltham, MA, USA). Results: Results were obtained from 889/901 (97%) biopsies with detection of EGFR mutations in 114/889 (13%) cases using the Idylla system. Among the 562 EGFR wild type tumors identified with Idylla, NGS detected one actionable and one nonactionable EGFR mutation. Conclusions: Rapid and targeted assessment of EGFR mutations in treatment-naïve NSLC can be implemented in routine clinical practice. However, it is mandatory to integrate this approach into a molecular algorithm that allows evaluation of potentially actionable genomic alterations other than EGFR mutations.

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