scholarly journals Successful Remedy With Osimertinib in a Patient of Thr790Met-positive Non-small Cell Lung Cancer With Leptomeningeal Carcinomatosis and Resistant to Gefitinib

2021 ◽  
Author(s):  
Liqing Xu ◽  
Shengli Shen ◽  
Hongzhou Duan
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitor ◽  
Leptomeningeal Metastasis ◽  
Leptomeningeal Carcinomatosis ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung

Abstract Patients of non-small cell lung cancer (NSCLC) with activated EGFR mutations is more apt to develop leptomeningeal metastasis (LM) than the other types of lung cancers [1]. Examination of circulating tumor DNA (ctDNA) in cell-free cerebrospinal fluid (CSF) has been shown to be useful in detecting the genomic mutations of tumors in central nervous system (CNS) and has also been used to monitor tumor progression and evaluate the response to treatments [2]. Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, is considered to be a recent standardized treatment for EGFR Thr790Met-mutant NSCLC because of its good efficacy in both systemic and CNS metastasis [3].

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.

Circulating Tumor DNA in Non–Small-Cell Lung Cancer: A Primer for the Clinician

2017 ◽  
pp. 1-13 ◽  
Author(s):  
Aditi P. Singh ◽  
Haiying Cheng ◽  
Xiaoling Guo ◽  
Benjamin Levy ◽  
Balazs Halmos
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Residual Disease ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Tumor Dna

Circulating tumor DNA (ctDNA) consists of short, double-stranded DNA fragments that are released into the circulation by tumor cells. With the advent of newer molecular platforms, ctDNA can be detected with high sensitivity and specificity in plasma. The assay’s noninvasive nature, ability to reflect intratumoral heterogeneity, short turnaround time, and ability to obtain serial samples make it an attractive option compared with traditional tissue biopsy tumor sequencing. Currently, this technology is mostly being used for the detection of EGFR mutations in patients with advanced non–small-cell lung cancer where tissue is inadequate to detect EGFR mutations that drive acquired resistance, most notably EGFR T790M. Emerging uses include the incorporation of ctDNA testing into primary diagnosis, treatment monitoring, detection of minimal residual disease, and detection of early-stage disease in screening populations. This review summarizes both validated and evolving uses of ctDNA testing in non–small-cell lung cancer in the context of oncologists’ daily practice and some of its potential challenges in the era of targeted therapy and immunotherapy.

scholarly journals Integrated Omics Analysis of Non-Small-Cell Lung Cancer Cells Harboring the EGFR C797S Mutation Reveals the Potential of AXL as a Novel Therapeutic Target in TKI-Resistant Lung Cancer

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 111
Author(s):  
Tong-Hong Wang ◽  
Chih-Ching Wu ◽  
Kuo-Yen Huang ◽  
Yann-Lii Leu ◽  
Shuenn-Chen Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitor ◽  
Cell Model ◽  
Small Cell ◽  
Egfr Mutations ◽  
Nsclc Cell Line ◽  
Small Cell Lung

Oncogenic mutations of epidermal growth factor receptor (EGFR) are responsive to targeted tyrosine kinase inhibitor (TKI) treatment in non-small-cell lung cancer (NSCLC). However, NSCLC patients harboring activating EGFR mutations inevitably develop resistance to TKIs. The acquired EGFR C797S mutation is a known mechanism that confers resistance to third-generation EGFR TKIs such as AZD9291. In this work, we employed CRISPR/Cas9 genome-editing technology to knock-in the EGFR C797S mutation into an NSCLC cell line harboring EGFR L858R/T790M. The established cell model was used to investigate the biology and treatment strategy of acquired EGFR C797S mutations. Transcriptome and proteome analyses revealed that the differentially expressed genes/proteins in the cells harboring the EGFR C797S mutation are associated with a mesenchymal-like cell state with elevated expression of AXL receptor tyrosine kinase. Furthermore, we presented evidence that inhibition of AXL is effective in slowing the growth of NSCLC cells harboring EGFR C797S. Our findings suggest that AXL inhibition could be a second-line or a potential adjuvant treatment for NSCLC harboring the EGFR C797S mutation.

scholarly journals Updated survival outcomes of NEJ005/TCOG0902: a randomised phase II study of concurrent versus sequential alternating gefitinib and chemotherapy in previously untreated non-small cell lung cancer with sensitive EGFR mutations

ESMO Open ◽  
2018 ◽  
Vol 3 (2) ◽  
pp. e000313 ◽  
Author(s):  
Satoshi Oizumi ◽  
Shunichi Sugawara ◽  
Koichi Minato ◽  
Toshiyuki Harada ◽  
Akira Inoue ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
First Line ◽  
Combination Strategy ◽  
North East

BackgroundThe North-East Japan Study Group (NEJ) 005/Tokyo Cooperative Oncology Group (TCOG) 0902 study has reported that first-line concurrent and sequential alternating combination therapies of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (gefitinib) plus platinum-based doublet chemotherapy (carboplatin/pemetrexed) offer promising efficacy with predictable toxicities for patients with EGFR-mutant non-small cell lung cancer. However, overall survival (OS) data were insufficient in the primary report because of the lack of death events.Patients and methodsProgression-free survival (PFS) and OS were re-evaluated at the final data cut-off point (March 2017) for the entire population (n=80).ResultsAt the median follow-up time of 35.6 months, 88.8% of patients had progressive disease and 77.5% of patients had died. Median PFS was 17.5 months for the concurrent regimen and 15.3 months for the sequential alternating regimen (P=0.13). Median OS was 41.9 and 30.7 months, respectively (P=0.036). Updated response rates were similar in both groups (90.2% and 82.1%, respectively; P=0.34). Patients with Del19 tumours displayed relatively better OS (median: 45.3 vs 33.3 months, respectively) than those with L858R (31.4 vs 28.9 months, respectively). No severe adverse events, including interstitial lung disease, occurred in the period since the primary report.ConclusionsThis updated analysis confirms that PFS is improved with first-line combination therapy compared with gefitinib monotherapy and that the concurrent regimen, in particular, offers an OS benefit of 42 months in the EGFR-mutated setting. Our ongoing NEJ009 study will clarify whether this combination strategy can be incorporated into routine clinical practice.Trial registration numberUMIN C000002789, Post-results.

scholarly journals An Improved Detection of Circulating Tumor DNA in Extracellular Vesicles-Depleted Plasma

2021 ◽  
Vol 11 ◽  
Author(s):  
Li Sun ◽  
Meijun Du ◽  
Manish Kohli ◽  
Chiang-Ching Huang ◽  
Xiaoxiang Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Extracellular Vesicles ◽  
Cell Lung Cancer ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Egfr Mutations ◽  
Plasma Samples ◽  
Small Cell Lung ◽  
Tumor Dna

Circulating tumor DNA (ctDNA) in plasma has been used as a biomarker for cancer detection and outcome prediction. In this study, we collected the five precipitates (fractions 1–5) and leftover supernatant plasma component (fraction 6) by a sequential centrifugation in plasma samples from nine small cell lung cancer (SCLC) patients. The fractions 3, 5 and 6 were large vesicles, exosomes and extracellular vesicles (EVs)-depleted plasma, respectively. Fragment size analysis using DNAs from these fractions showed dramatical differences from a peak of 7–10 kb in fraction 1 to 140–160 bp in fraction 6. To determine ctDNA content, we performed whole genome sequencing and applied copy number-based algorithm to calculate ctDNA percentage. This analysis showed the highest ctDNA content in EV-depleted plasma (average = 27.22%), followed by exosomes (average = 22.09%) and large vesicles (average = 19.70%). Comparatively, whole plasma, which has been used in most ctDNA studies, showed an average of 23.84% ctDNA content in the same group of patients. To further demonstrate higher ctDNA content in fraction 6, we performed mutational analysis in the plasma samples from 22 non-small cell lung cancer (NSCLC) patients with known EGFR mutations. This analysis confirmed higher mutation detection rates in fraction 6 (14/22) than whole plasma (10/22). This study provides a new insight into potential application of using fractionated plasma for an improved ctDNA detection.

Phase II study of the efficacy of gefitinib in patients with non-small cell lung cancer with the EGFR mutations

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7183-7183 ◽  
Author(s):  
N. Sunaga ◽  
N. Yanagitani ◽  
K. Kaira ◽  
Y. Tomizawa ◽  
H. Iijima ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Survival Data ◽  
Kinase Inhibitor ◽  
Direct Sequencing ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Grade 3

7183 Purpose: Recent studies have indicated that the mutations of epidermal growth factor receptor (EGFR) were associated with sensitivity of non-small cell lung cancer (NSCLC) to gefitinib, an EGFR tyrosine kinase inhibitor. The clinical objective of this study was to prospectively evaluate the efficacy of gefitinib in patients with stageIII/IV NSCLC that had the EGFR mutations. Methods: Genomic DNA was extracted from tumor specimens and EGFR mutations in exon 19 and 21 were analyzed by direct sequencing. Patients with stageIII/IV NSCLC who had the EGFR mutations were treated with gefitinib (250mg) orally. Response, survival data and toxicity were assessed. Results: From Nov. 2004 to Dec 2005, 14 patients with the EGFR mutations received gefitinib (median age: 67 years; 2 males, 12 females; 1 smokers, 13 non-smokers; all adenocarcinomas). Two patients discontinued gefitinib and came off study because of interstitial pneumonitis (grade 3) and acne (grade 3), respectively. Response data are available for 12 patients. Two achieved a complete response (CR), seven exhibited a partial response (PR) and three had stable disease (SD). Response rate and disease control rate were 75% and 100%, respectively. There were no grade 3/4 toxicities in these 12 patients. All patients were alive during median follow-up period of 8 months (range 1–13 months). Conclusions: The EGFR mutations could be an excellent predictor of response to gefitinib in NSCLC. No significant financial relationships to disclose.

Gefitinib in Non-Small Cell Lung Carcinoma: A Case Report of an Unusual Side Effect and Complete Response in Advanced Disease

2013 ◽  
Vol 99 (1) ◽  
pp. e3-e5 ◽  
Author(s):  
Maria Maddalena Laterza ◽  
Bruno Chiurazzi ◽  
MariaFiorella Brangi ◽  
Ferdinando Riccardi ◽  
Giacomo Cartenì
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Side Effect ◽  
Kinase Inhibitor ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

Gefitinib is a tyrosine kinase inhibitor, indicated in advanced non-small cell lung cancer in all lines of treatment for patients harboring EGFR mutations. It has a favorable toxicity profile but may induce unexpected adverse effects, such as an infiammatory reaction in the bladder. We report a rare case of hemorrhagic cystitis, an unusual side effect, in a patient with non-small cell lung cancer treated with gefitinib, which did not compromise the clinical response.

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