Relative Abundance of EGFR Mutations Predicts Benefit From Gefitinib Treatment for Advanced Non–Small-Cell Lung Cancer

2011 ◽  
Vol 29 (24) ◽  
pp. 3316-3321 ◽  
Author(s):  
Qing Zhou ◽  
Xu-Chao Zhang ◽  
Zhi-Hong Chen ◽  
Xiao-Lu Yin ◽  
Jin-Ji Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Sequencing ◽  
Small Cell Lung Cancer ◽  
Egfr Mutation ◽  
Small Cell ◽  
Egfr Mutations ◽  
Wild Type ◽  
Small Cell Lung ◽  
Direct Dna Sequencing ◽  
Gefitinib Treatment

Purpose Our aim was to determine whether abundance of epidermal growth factor receptor (EGFR) mutations in tumors predicts benefit from treatment with EGFR–tyrosine kinase inhibitors (TKIs) for advanced non–small-cell lung cancer (NSCLC). Patients and Methods We detected EGFR mutations in 100 lung cancer samples using direct DNA sequencing and amplification refractory mutation system (ARMS). Mutation-positive tumors by both methods carried high abundance of EGFR mutations. Tumors that were mutation positive by ARMS but mutation negative by direct DNA sequencing harbored low abundance of EGFR mutations. Mutation-negative tumors by both methods carried wild-type EGFR. All patients received gefitinib treatment. The correlation between EGFR mutation abundance and clinical benefit from gefitinib treatment was analyzed. Results Of 100 samples, 51 and 18 harbored high and low abundances of EGFR mutations, respectively; 31 carried wild-type EGFR. Median progression-free survival (PFS) was 11.3 (95% CI, 7.4 to 15.2) and 6.9 months (95% CI, 5.5 to 8.4) in patients with high and low abundances of EGFR mutations, respectively (P = .014). Median PFS of patients with low abundance of EGFR mutations was significantly longer than that of those with wild-type tumors (2.1 months; 95% CI, 1.0 to 3.2; P = .010). Objective response rates (ORRs) were 62.7%, 44.4%, and 16.1%, and overall survival (OS) rates were 15.9 (95% CI, 13.4 to 18.3), 10.9 (95% CI, 2.7 to 19.1), and 8.7 months (95% CI, 4.6 to 12.7) for patients with high abundance of EGFR mutations, low abundance of EGFR mutations, and wild-type EGFR, respectively. The difference between patients with high and low abundances of EGFR mutations was not significant regarding ORR and OS. Conclusion The relative EGFR mutation abundance could predict benefit from EGFR-TKI treatment for advanced NSCLC.

EGFR mutation analysis in histologic and cytologic specimens of non-small cell lung cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7176-7176 ◽  
Author(s):  
H. Sakai ◽  
K. Akagi ◽  
J. Sudoh ◽  
S. Yoneda ◽  
H. Komagata ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Mutation Analysis ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Polymorphism Analysis ◽  
Small Cell Lung

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.

ALK and EGFR mutation analysis in a phase II trial of cisplatin/pemetrexed in Japanese patients with advanced nonsquamous non-small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18017-e18017
Author(s):  
Kyohei Kaburaki ◽  
Fumiyoshi Ohyanagi ◽  
Azusa Tanimoto ◽  
Toshio Sakatani ◽  
Yuko Kawano ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Response Rate ◽  
Fusion Gene ◽  
Objective Response ◽  
Small Cell ◽  
Wild Type ◽  
Small Cell Lung

e18017 Background: Recently, ethnic differences and genotypes such as EGFR mutation (EGFRm) or fusion gene (ALK translocation: ALKt) are important factors in non-small cell lung cancer (NSCLC) treatment. Pemetrexed (P)/cisplatin (C) is one of the standard care for advanced non-squamous (Nsq) NSCLC. However, the efficacy of the CP regimen has not been well examined in Japanese Nsq NSCLC patients (pts); furthermore, the difference in efficacy between genotypes was not thoroughly examined. Therefore, the present study was conducted to evaluate the efficacy of the CP regimen in Japanese Nsq NSCLC pts, and to determine whether EGFRm and ALKt impacted the treatment. Methods: This study was conducted from May 2009 to December 2010. Pts were eligible for this study if they had histologically or cytologically confirmed recurrent or metastatic Nsq NSCLC previously untreated with chemotherapy, an ECOG performance status of 0 or 1, life expectancy of more than 12 weeks, and adequate organ function. Pts received C (75 mg/m2) plus P (500 mg/m2) on day 1 every 3 weeks. Of the 50 pts initially enrolled, 49 were evaluated, and 43 tumor samples were available for analysis. Most pts were male (80%), and 80% of the pts had adenocarcinoma. The primary endpoint was the response rate that was evaluated according to RECIST. EGFRm was examined using PCR-based methods, and the ALK fusion protein was examined using a highly sensitive IHC method in the available tumor specimens. Although the CP regimen demonstrates consistent efficacy in Japanese Nsq NSCLC pts, EGFRm and ALKt may have impacted this treatment. Results: The objective response rate and disease control rate in all pts were 44.9% and 79.6%, respectively. The median progression-free survival was 4.4 months, and the 1-year survival was 73.5%. Toxicities were mild; no new toxicity profile was identified. Among the 43 samples, the following mutations were identified: 9 EGFRm (21%), 5 ALKt (12%), and 29 wild-type (67%). Objective response was observed in 6 (66.7%) EGFRm, 2 (40%) ALKt, and 13 (44.8%) wild-type. Conclusions: Although the CP regimen demonstrates consistent efficacy in Japanese Nsq NSCLC pts, EGFRm and ALKt may have impacted this treatment.

Neratinib, an Irreversible Pan-ErbB Receptor Tyrosine Kinase Inhibitor: Results of a Phase II Trial in Patients With Advanced Non–Small-Cell Lung Cancer

2010 ◽  
Vol 28 (18) ◽  
pp. 3076-3083 ◽  
Author(s):  
Lecia V. Sequist ◽  
Benjamin Besse ◽  
Thomas J. Lynch ◽  
Vincent A. Miller ◽  
Kwok K. Wong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Objective Response ◽  
Resistance Mutation ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung

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.

Assessment of EGFR mutations in patients diagnosed of squamous non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18106-e18106
Author(s):  
Francisco Lobo ◽  
Manuel Domine ◽  
Federico Rojo ◽  
Yann Izarzugaza ◽  
Ana Leon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Exon 20 ◽  
Nsclc Patients

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.

EGFR mutation status of cell free serum DNA and clinical efficacy of afatinib in pretreated non-small cell lung cancer (NSCLC) harboring EGFR mutations.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e19087-e19087
Author(s):  
Satoru Kitazono ◽  
Hironari Nishizawa ◽  
Hiroshi Kobayashi ◽  
Tomoyo Oguri ◽  
Yuichi Tambo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Efficacy ◽  
Egfr Mutation ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Mutation Status ◽  
Serum Dna ◽  
Free Serum

EGFR Exon 20 insertion: Prognostic and predictive values in advanced non-small cell lung cancer, a real-world study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9062-9062
Author(s):  
Christos Chouaid ◽  
Thomas Filleron ◽  
Didier Debieuvre ◽  
Maurice Perol ◽  
Nicolas Girard ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Real World ◽  
Small Cell ◽  
Egfr Mutations ◽  
Wild Type ◽  
Small Cell Lung ◽  
First Line ◽  
Exon 20

9062 Background: In Europe, 10-15% of non-squamous non-small cell lung cancer (nsqNSCLC) have EGFR mutations of which 5-12% are an Exon 20 insertion (20ins). Methods: Analysis of Epidemio-Strategy and Medical Economics (ESME) Advanced and Metastatic Lung cancer (AMLC) Data Platform (NCT03848052), a multicenter real-life database using a supervised, retrospective data collection process. The database includes 13737 advanced nsqNSCLC treated from January 2015 at participating centres. The cut-off date for patient follow-up for this analysis was June 30, 2020. The aim of the study was to assess real-world patient characteristics, treatment patterns and clinical outcomes of advanced nsqNSCLC EGFR 20ins. Overall survival (OS) of EGFR cohorts (20ins, 19del/L858R without 20ins, other EGFR mutations) and EGFR wild-type/not tested cohort were assessed. Results: 1549 (11.3%) nsqNSCLC had an EGFR mutation, 61 (3.9%) of whom being an EGFR 20ins. These 61 patients (pts) are mainly female (68.9%), non-smoker (55.7%), with de novo stage IIIB/IV disease (78.6%), PS 0-1 (76.9%). Median age was 68.0 years (q1-q3: 54-74). PD-L1 status was assessed in 34 (55.7%) pts, mainly (n = 20) before first line and 22 (64.7%) had negative result. Most (63.9%) pts had EGFR 20ins positive result available before first line. Almost all pts (95.1%, n = 58) received a systemic therapy with a median number of 3 (q1-q3: 1-4) lines. In first line setting, 74% of the pts received chemotherapy (mainly chemotherapy combination), 13.7% received EGFR TKI (mainly as monotherapy) and 8.6% received immunotherapy only. Median treatment duration for pts treated with CarboPem (n = 19), CisplatinPem (n = 16) and CarboTaxol (n = 6) were 4.7 (q1-q3: 2.6-6.6), 7.4 (q1-q3: 5.0-12.8) and 3.3 (q1-q3: 2.8-3.8) months, respectively. For afatinib (n = 3), erlotinib (n = 2) and gefitinib (n = 1), median treatment durations were 1.6 (q1-q3: 0.5-2.8); 1.8 (q1-q3: 1.4-2.1) and 2.3 months, respectively. After a median follow up of 36.3 (95%CI: 34.1-39.8) months, median OS was 24.3 (95%CI: 19.1-32.6) months; 1 and 2-years OS rates were 82.5% (95%CI: 69.7-90.2) and 52.6% (95%CI: 37.3-65.9), respectively. For pts with 19del/L858R without 20ins (n = 1049) and those with other EGFR mutations (n = 439) median OS were 35.4 (95%CI: 32.6-37.5) and 41.7 (95%CI: 31.9-53.5), respectively compared to 20.7 (95%CI: 20.0-21.8] months for pts EGFR wild type/not tested (n = 12188). Conclusions: This large, national real-world analysis based on medical chart data’s confirm that EGFR 20ins is a rare disease (0.4% of advanced nsqNSCLC). Currently available EGFR TKIs appear to have low efficacy and response to chemotherapy seems identical to that of EGFR wild-type/not tested pts. Prognosis for NSCLC pts with EGFR 20ins mutations was in line with that of EGFR wild type/not tested but worse than common EGFR mutations highlighting the need for advancements for this rare population.

Miliary brain metastases in 2 cases with advanced non-small cell lung cancer harboring EGFR mutation during gefitinib treatment

2012 ◽  
Vol 50 (3) ◽  
pp. 117-121 ◽  
Author(s):  
Sayaka Mochizuki ◽  
Naoki Nishimura ◽  
Akira Inoue ◽  
Koji Murakami ◽  
Toshihiro Nukiwa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Small Cell ◽  
Small Cell Lung ◽  
Gefitinib Treatment

scholarly journals Body Mass Index, Weight Loss, and Mortality Risk in Advanced-Stage Non-Small Cell Lung Cancer Patients: A Focus on EGFR Mutation

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3761
Author(s):  
Yu-Mu Chen ◽  
Chien-Hao Lai ◽  
Chiung-Yu Lin ◽  
Yi-Hsuan Tsai ◽  
Ya-Chun Chang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Body Mass Index ◽  
Weight Loss ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Small Cell ◽  
Wild Type ◽  
Small Cell Lung ◽  
Nsclc Patients

Body mass index (BMI) influences the prognosis of patients with non-small cell lung cancer (NSCLC), including both early-stage and late-stage NSCLC patients that are undergoing chemotherapies. However, earlier research on the relationship between BMI and survival in patients taking epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) yielded contradictory results. These publications either had a limited number of patients or were getting TKIs in various lines of therapy, which might explain why the outcomes were contradictory. As a result, we undertook retrospective study to examine the effect of BMI on survival outcomes in patients with advanced EGFR mutant NSCLC receiving first-line EGFR-TKIs. We also compared the findings to those with wild-type EGFR. Between November 2010 and March 2014, 513 patients with advanced NSCLC were enrolled in the study. According to the adjusted BMI cut-off point for Asia, 35 out of 513 (6.8%) patients were underweight (BMI < 18.5 kg/m2), whereas 197 (38.4%) were overweight (BMI > 24 kg/m2). Overweight patients with wild-type EGFR exhibited longer progression-free survival (4.6 vs. 2.1 months, p = 0.003) and overall survival (OS) (8.9 vs. 4.3 months, p = 0.003) than underweight patients. Overweight patients with EGFR mutations had a longer OS than normal-weight patients (23.0 vs. 20.2 months, p = 0.025). Bodyweight reduction was related to a shorter OS in both the mutant EGFR patients (17.1 vs. 30.5 months, p < 0.001) and the wild-type EGFR patients (7.8 vs. 18.7 months, p < 0.001). In conclusion, advanced stages NSCLC patients with a lower BMI and early weight loss had a worse outcome that was independent of EGFR mutation status.

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