Epidermal growth factor receptor (EGFR) mutation testing in non-small cell lung cancer (NSCLC) patients (pts)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7177-7177
Author(s):  
L. V. Sequist ◽  
V. A. Joshi ◽  
P. A. Jänne ◽  
P. Fidias ◽  
A. Muzikansky ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Mutation Screening ◽  
Growth Factor Receptor ◽  
Routine Care ◽  
Response To Therapy ◽  
Smoking History ◽  
Egfr Mutations ◽  
Unresectable Disease

7177 Background: Somatic mutations in EGFR are associated with response to therapy and prolonged overall survival (OS) of NSCLC pts treated with tyrosine kinase inhibitors (TKI). We began EGFR mutation screening in 2004 with a CLIA certified test. We determined the characteristics of pts tested, EGFR mutations identified, and analyzed response to therapy and OS. Methods: We performed a retrospective cohort study of all NSCLC pts referred for EGFR testing over 1 year. Samples underwent direct sequence analysis of EGFR exons 18–24. We used multivariable logistic regression models to examine associations between mutation and pt characteristics. We used chi-square tests to assess differences in response to therapy by EGFR status and analyzed OS with Cox proportional hazard models, adjusting for age, gender and stage. Results: We screened 269 NSCLC pts for EGFR mutations, including 188 (71%) with unresectable disease and 245 (91%) with adenocarcinoma. Mutations were identified in 62 (23%) pts. 15 samples (6%) yielded insufficient DNA for testing. Mutation was more likely in the 59 never-smokers compared to the 185 ever-smokers [odds ratio (OR) 4.8, 95% confidence interval (CI) 2.5–9.2]. Each added pack-year of smoking history lowered the odds of mutation by 5% (OR 0.95, 95% CI 0.94–0.97). Mutation was more likely in the 12 Asians than in the 212 of all other races (OR 3.7, 95% CI 1.1–12.0). In multivariable analyses, pack-years of smoking remained predictive of mutation (OR 0.96, 95% CI 0.94–0.99). Among 44 pts with unresectable disease undergoing subsequent TKI therapy, the 20 EGFR positive pts had an increased response rate (RR) compared to the 24 EGFR negative pts (60% v. 4%, p < 0.0001). In 27 pts given subsequent chemotherapy, RR was 33% and did not differ by EGFR status. Median follow-up was 9.8 months (mo) (range 0.2–135.8 mo). Among pts with unresectable disease, median OS is estimated to be 22.7 mo in EGFR negative pts and is not reached in EGFR positive pts (HR 0.22, 95% CI 0.80–0.63). Conclusions: Sequencing EGFR for somatic mutations is feasible in routine care of NSCLC pts. 23% of screened pts tested positive, and never smoking was the strongest predictor of mutation. Among patients with unresectable disease, EGFR mutation was associated with an increased RR to TKI therapy and OS. [Table: see text]

EGFR mutation analysis and treatment outcomes with tyrosine kinase inhibitors in EGFR mutants: The Manchester Lung Cancer Group Experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18095-e18095
Author(s):  
Rahul Peck ◽  
Elizabeth Connolly ◽  
Paul Taylor ◽  
Corinne Faivre-Finn ◽  
Fiona Hellen Blackhall ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Response To Treatment ◽  
Smoking History ◽  
Egfr Mutations ◽  
Published Data ◽  
Duration Of Treatment

e18095 Background: The presence of Epidermal Growth Factor Receptor (EGFR) activating mutations in patients with NSCLC was first described in 2005. Tumours exhibiting these mutations show sensitivity to treatment with an oral Tyrosine Kinase Inhibitor. Testing for EGFR mutations in patients with non-squamous NSCLC began in the Greater Manchester and Cheshire network in the last quarter of 2009. Methods: We audited the notes of consecutive patients who were identified with an activating EGFR mutation by the Central Manchester Genetics Laboratory between November 2009 and October 2011. Results: A total of 110 mutations were identified in tumour tissue from 98 patients. 13.6% were in exon 18, 38.2% in exon 19, 15.4% in exon 20 and 32.8% in exon 21. 65% of patients were female. The median age was 69 years (36-89). Notes were available for 85 patients, 59 of whom received treatment with an EGFR TKi. 7 had previously received radical treatment and 19 never received treatment. 7% were current smokers, 40% were ex-smokers, 30.6% had never smoked and smoking history was not documented in 22.4%. An initial response to treatment was seen in 55%, with stable disease in 15%.The mean duration of treatment was 7.6 months (2 weeks – 23 months), with 24 patients still receiving a TKi at the time of data analysis. The most commonly seen toxicities were diarrhoea and rash. Only 1 patient had no documented toxicity from their TKi. 17 patients (29%) had treatment discontinued or interrupted because of toxicity. In 8 of these, treatment was re-introduced at a reduced dose, and 3 patients went back to full dose. Conclusions: Our results confirm that treatment with a TKi is effective for those patients whose tumours harbour EGFR mutations, with a side effect profile consistent with published data.

Surrogate Predictive Biomarkers for Response to Anti-EGFR Agents: State of the Art and Challenges

2007 ◽  
Vol 22 (1_suppl4) ◽  
pp. 10-23 ◽  
Author(s):  
F. Cappuzzo ◽  
L. Toschi ◽  
G. Finocchiaro ◽  
C. Ligorio ◽  
A. Santoro
Keyword(s):  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Smoking History ◽  
Egfr Mutations ◽  
Gene Gain ◽  
Biological Variables ◽  
Drug Receptor ◽  
Exon 20

The epidermal growth factor receptor (EGFR) plays a key role in cancer development and progression in several human malignancies including non-small cell lung cancer (NSCLC). Several strategies aimed at inhibiting the EGFR have been investigated in the last years, including the use of small tyrosine kinase inhibitors (TKIs) directed against the intracellular domain of the receptor and monoclonal antibodies targeting its extracellular portion. Subgroups of patients who are more likely to respond to TKIs have been identified based on both clincal and biological features. Never-smoking history has emerged as the most relevant clinical characteristic predictive of response to TKIs in NSCLC, while presence of drug-sensitive EGFR mutations and EGFR gene gain represent critical biological variables associated with an improved outcome for patients exposed to these agents. Recent studies have highlighted the existence of biological factors involved in intrinsic and acquired resistance to TKIs, including k-ras, HER-2 and EGFR exon 20 mutations. Increasing knowledge of EGFR biology and drug-receptor interactions will allow to identify individuals who are likely to derive a clinical benefit from the proposed targeted therapy, sparing refractory patients expensive and potentially toxic treatment.

scholarly journals EGFR Mutations in Latinos From the United States and Latin America

2016 ◽  
Vol 2 (5) ◽  
pp. 259-267 ◽  
Author(s):  
Ariel Lopez-Chavez ◽  
Anish Thomas ◽  
Moses O. Evbuomwan ◽  
Liqiang Xi ◽  
Guinevere Chun ◽  
...  
Keyword(s):  
United States ◽  
Latin America ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Clinical Laboratory ◽  
Growth Factor Receptor ◽  
The United States ◽  
Egfr Mutations ◽  
Significant Difference ◽  
Egfr Tyrosine Kinase Inhibitors

Purpose Epidermal growth factor receptor (EGFR) mutations confer sensitivity to EGFR tyrosine kinase inhibitors in patients with advanced non–small-cell lung cancer (NSCLC). There are limited and conflicting reports on the frequency of EGFR mutations in Latinos. Patients and Methods Samples from 642 patients with NSCLC from seven institutions in the United States and Latin America were assessed for EGFR mutations (exons 18 to 21) at Clinical Laboratory Improvement Amendments-certified central laboratories. Results EGFR mutation analysis was successfully performed in 480 (75%) of 642 patients; 90 (19%) were Latinos, 318 (66%) were non-Latino whites, 35 (7%) were non-Latino Asians, 30 (6%) were non-Latino blacks, and seven (2%) were of other races or ethnicities. EGFR mutations were found in 21 (23%) of 90 Latinos with varying frequencies according to the country of origin; Latinos from Peru (37%), followed by the United States (23%), Mexico (18%), Venezuela (10%), and Bolivia (8%). In never-smoker Latinos and Latinos with adenocarcinoma histology, EGFR mutation frequencies were 38% and 30%, respectively. There was a significant difference in the frequency of EGFR mutations among the different racial and ethnic subgroups analyzed (P < .001), with non-Latino Asians having the highest frequency (57%) followed by Latinos (23%), non-Latino whites (19%), and non-Latino blacks (10%). There was no difference between Latinos (23%) and non-Latinos (22%; P = .78) and Latinos and non-Latino whites (P = .37). Patients from Peru had an overall higher frequency of mutations (37%) than all other Latinos (17%), but this difference only exhibited a trend toward significance (P = .058). Conclusion There was no significant difference between the frequency of EGFR mutations in NSCLC in Latinos and non-Latinos.

Correlation of gefitinib efficacy and detection of new EGFR mutation variants in pre-treated patients (pts) with advanced non- small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18062-18062
Author(s):  
A. Pallis ◽  
A. Voutsina ◽  
A. Kalikaki ◽  
A. Koutsopoulos ◽  
J. Souglakos ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Direct Sequencing ◽  
Growth Control ◽  
Smoking History ◽  
Egfr Mutations ◽  
Egfr Gene ◽  
Formalin Fixed Paraffin ◽  
Gefitinib Treatment ◽  
Low Incidence

18062 Background: The efficacy of tyrosine kinase inhibitors (TKIs) of EGFR is associated with well characterized mutations on the exons 18, 19 and 21 of EGFR gene. Less common mutations could be detected in these exons but their relationship with the clinical efficacy of TKIs has not been established yet. Methods: Genomic DNA was extracted from microdissected formalin-fixed paraffin-embeded tumor tissue from 86 pts enrolled in a gefitinib expanded access program. Exons 18, 19 and 21 were amplified and subjected to direct sequencing. Results: Classical EGFR mutations (CM) were detected in 9 (10.4%) pts and other mutations variants (MV) in 19 (22%) pts. Eight (42.1%) MV were observed in exon 18, 3 (15.8%) in exon 19 and 8 (42.1%) in exon 21. Tumor Growth Control (TGC) was achieved in 88.9% (3PR and 5SD) pts with CM, 63% (2PR and 10SD) pts with MV and in 45.9% (3PR and 25SD) pts with wild type EGFR gene (WT). There was no clear association between the presence of EGFR MV and the sex, histology or smoking history. The median TTP was 64 weeks (range:4- 80+), 20 weeks (range:6–140) and 16 weeks (range:4–176+) in pts with CM, MV and WT, respectively. Nine (47.3%) pts with EGFR MV had a TTP >24 weeks. The median survival was 78 weeks (range:5–94+), 70 weeks (range:10–142) and 36 weeks (range:4–176+) in pts with CM, MV and WT, respectively. Three patients bearing mutations in exons 18, 19, and 21 progressed despite gefitinib treatment suggesting that these mutations could be related to resistance to gefitinib. Conclusions: EGFR mutation variants could be associated with response or resistance to TKIs but their low incidence requires their evaluation in a largest cohort of patients. No significant financial relationships to disclose.

Circulating tumor DNA (ctDNA) to monitor treatment response and progression in patients treated with tyrosine kinase inhibitors (TKIs) and immunotherapy for EGFR-mutant non-small cell lung cancer (NSCLC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20652-e20652 ◽  
Author(s):  
Brian S. Henick ◽  
Sarah B. Goldberg ◽  
Azeet Narayan ◽  
Chiara Rossi ◽  
Simon Rodney ◽  
...  
Keyword(s):  
Disease Progression ◽  
Kinase Inhibitors ◽  
Radiographic Progression ◽  
Egfr Mutation ◽  
Circulating Tumor Dna ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Egfr Mutations ◽  
Quantitative Changes ◽  
Egfr Mutant

e20652 Background: Detection of EGFR mutations in ctDNA can help determine appropriateness of TKI therapy for patients with NSCLC. We investigated whether longitudinal monitoring of ctDNA levels can be used to assess response to therapy and disease progression, with a focus on EGFR mutation-positive patients treated with immunotherapy. Methods: Serially collected blood from patients with EGFR mutation-positive NSCLC treated with TKIs and/or immunotherapy was analyzed using an ultrasensitive 24-gene next-generation sequencing assay. Clinical characteristics and outcomes were analyzed retrospectively by chart review. Results: We studied quantitative changes in ctDNA levels during treatment by analyzing somatic mutations in 91 plasma samples from 8 patients with EGFR-mutant NSCLC, including samples collected around the time of disease progression for a subset of patients. Two patients treated with PD-1 inhibitor monotherapy experienced a rise in ctDNA harboring EGFR-sensitizing mutations prior to radiographic progression. A third patient was started on anti-PD-1 monotherapy following disease progression on erlotinib. Plasma levels of L858R, T790M, and TP53 mutations were detectable on treatment initiation and decreased with radiographic response. The levels of these mutations rose at progression,fell with response to EGFR-directed therapy, and increased again before disease progression. Another patient was found to have mutations in EGFR, T790M, and TP53 that fell upon treatment with combination TKI therapy. The remaining four patients studied were treated with concurrent TKI and immunotherapy. In all of these cases, sensitizing EGFR mutations were present in plasma at low levels during response to treatment. Two of the four patients had a rise in ctDNA level at the time of radiographic progression; the other two patients had durable responses with persistently low ctDNA levels. Analysis of additional cases is ongoing. Conclusions: Monitoring quantitative changes in ctDNA may enable assessment of response or disease progression in immunotherapy- and TKI-treated EGFR-mutant NSCLC patients.

scholarly journals Association between EGFR mutation status, clinicopathological characteristics and TTF-1 expression in lung adenocarcinoma - a single center study

2020 ◽  
pp. 111-111
Author(s):  
Dragana Tegeltija ◽  
Aleksandra Lovrenski ◽  
Tijana Vasiljevic ◽  
Sinisa Maksimovic
Keyword(s):  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Clinicopathological Characteristics ◽  
Smoking History ◽  
Egfr Mutations ◽  
Exact Test ◽  
Thyroid Transcription Factor ◽  
Tumor Tissues ◽  
Single Center Study ◽  
Lung Adenocarcinomas

Introduction/Objective. The presence of EGFR mutations is the best predictor of response for therapy with tyrosine kinase inhibitors. In this study we investigate association between EGFR mutations and clinicopathological characteristics and thyroid transcription factor (TTF-1) expression in lung adenocarcinomas (ADs). Methods. We analyzed 142 surgical samples from patients with histologically confirmed lung ADs from January, 2010. to December, 2015. All tumor tissues were reclassified according to WHO criteria and EGFR mutations detected by Real time PCR. TTF-1 expression was detected by immunohistochemistry in 83 out of 142 cases. The association between EGFR and TTF-1 expression was analyzed using ?2 test or Fisher?s exact test with SPSS software version 20.0. Results. This study included 78 male and 64 women with a median age 61.6 (range, 42-82) years. Acinar (ACN) and solid (SOL) were the most common histological types (47.9% and 38.7% respectively). TTF-1 expression was present in 69 of 83 (83%) ADs. The EGFR mutation was found in 7%, more frequently in women, and patients with smoking history, and acinar type of ADs, whereas it had no association with age and pathological stage and TTF-1 expression. Conclusion. In conclusion, the results of this study demonstrate that the presence of EGFR mutations is associated with some clinical characteristics and histologic type of ADs, but not with TTF-1 expression.

scholarly journals Iterative Upgrading of Small Molecular Tyrosine Kinase Inhibitors for EGFR Mutation in NSCLC: Necessity and Perspective

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1500
Author(s):  
Jing Zhu ◽  
Qian Yang ◽  
Weiguo Xu
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Gene Mutations ◽  
Egfr Mutations ◽  
Convenient Route ◽  
Epidermal Growth ◽  
Nsclc Patients ◽  
Genome Information

Molecular targeted therapy has been reported to have fewer adverse effects, and offer a more convenient route of administration, compared with conventional chemotherapy. With the development of sequencing technology, and research on the molecular biology of lung cancer, especially whole-genome information on non-small cell lung cancer (NSCLC), various therapeutic targets have been unveiled. Among the NSCLC-driving gene mutations, epidermal growth factor receptor (EGFR) mutations are the most common, and approximately 10% of Caucasian, and more than 50% of Asian, NSCLC patients have been found to have sensitive EGFR mutations. A variety of targeted therapeutic agents for EGFR mutations have been approved for clinical applications, or are undergoing clinical trials around the world. This review focuses on: the indications of approved small molecular kinase inhibitors for EGFR mutation-positive NSCLC; the mechanisms of drug resistance and the corresponding therapeutic strategies; the principles of reasonable and precision molecular structure; and the drug development discoveries of next-generation inhibitors for EGFR.

scholarly journals Lower lymphocyte percentage and higher platelet count as poor prognostic factors for patients with epidermal growth factor receptor–mutated lung adenocarcinoma receiving tyrosine kinase inhibitors as first-line treatment

2019 ◽  
Author(s):  
Yi-Feng Wu ◽  
Chih-Bin Lin ◽  
Sung-Chao Chu ◽  
Wei-Han Huang ◽  
Jen-Jyh Lee ◽  
...  
Keyword(s):  
Platelet Count ◽  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Smoking History ◽  
Line Treatment ◽  
First Line ◽  
Epidermal Growth ◽  
First Line Treatment

Abstract Background This study evaluated the effect of clinical factors on the treatment outcomes of patients with lung adenocarcinoma with active epidermal growth factor receptor (EGFR) mutations who received tyrosine kinase inhibitors (TKIs) as first-line treatment. Methods Patients with stage IIIb or IV lung adenocarcinoma with mutated EGFR were enrolled retrospectively between March 2010 and December 2017. The effects of various clinical features and hematologic markers on progression-free survival (PFS) and overall survival (OS) were analyzed. Results A total of 190 patients were enrolled in this study. In univariate analysis, the male sex, smoking history, EGFR mutation with L858R, and presentation with malignant pleural effusion at initial diagnosis were significantly associated with shorter PFS or OS. Among hematologic markers, lower lymphocyte percentage and higher platelet count were associated with significantly poor PFS and OS. Stepwise multivariate Cox regression analysis showed that smoking history, EGFR mutation with L858R, and lower lymphocyte percentage were independent poor prognostic factors for PFS and OS. Presentation with malignant pleural effusion and higher platelet count was an independent poor prognostic factor for OS only. Conclusion Patients with lung adenocarcinoma receiving TKIs as the first-line treatment and having hematologic markers with lower lymphocyte percentage, and higher platelet count had poorer prognoses compared with other patients. Additional studies are warranted to elucidate the underlying mechanisms.

The SELECT study: A multicenter phase II trial of adjuvant erlotinib in resected epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7010-7010 ◽  
Author(s):  
Joel W. Neal ◽  
Nathan A. Pennell ◽  
Ramaswamy Govindan ◽  
Michael Lanuti ◽  
Rachel Pam Greenerger Rosovsky ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Early Stage ◽  
Prospective Trial ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Egfr Mutations ◽  
Resected Stage ◽  
Iiia Nsclc ◽  
Egfr Mutant

7010 Background: Cancers with activating EGFR mutations are exquisitely sensitive to EGFR tyrosine kinase inhibitors (TKIs) and retrospective data suggests adjuvant TKIs may improve outcomes in EGFR mutants. This prospective trial investigates the safety and efficacy of adjuvant erlotinib in EGFR mutation-positive NSCLC. Methods: Patients (pts) with surgically resected stage IA-IIIA NSCLC harboring activating EGFR mutations were treated with 150 mg/day of erlotinib for 2 years (y) after completion of any standard adjuvant chemotherapy and/or radiotherapy. The trial was designed to enroll 36 patients, and powered to demonstrate a primary endpoint of 2 y disease free survival (DFS) exceeding 85%, which would suggest improvement over the historically expected 70% 2 y DFS in early stage EGFR-mutant NSCLC (J Thorac Oncol 6:569). Results: Thirty-six pts were enrolled at five sites between 1/08 and 11/09; 53% stage I; 19% stage II; 28% stage IIIA. Toxicities were typical of erlotinib; no grade 4 or 5 events or pneumonitis occurred. 8 pts (22%) required one dose reduction to 100 mg/day and 5 (14%) two reductions to 50 mg/day for grade 3 or persistent grade 2 toxicities. 11 pts discontinued before 2 full years (<1 month (mo) [4], 1-12 mo [2] and 12-23 mo [5]) for toxicities [6], patient preference [3], prostate cancer [1] and recurrence [1]. After a median follow-up of 2.5 y, the 2 y DFS from enrollment is 94% (95% CI 80%, 99%). 10 patients have recurred, 1 during erlotinib treatment and the others after stopping erlotinib (interval before recurrence 2 mo [1], 6-12 mo [4], >12 mo [4]). Genotyping on repeat biopsies from seven of the recurrent cases is underway, as is assessment of response to subsequent erlotinib therapy. Two pts have died of recurrence: one at 1.5 y who stopped erlotinib after 1 mo for toxicity, and one at 2 y who progressed while on erlotinib. Conclusions: This is the first prospective study to report the efficacy of adjuvant erlotinib in NSCLC pts with EGFR mutations. This approach is feasible and yields excellent 2y DFS compared to historical genotype-matched controls. This trial was subsequently expanded to 100 pts to permit subgroup analysis by stage.

Sign in / Sign up

Export Citation Format

Share Document