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Treatment of EGFR T790M-Positive Non-Small Cell Lung Cancer

AbstractThe treatment of lung cancer has changed dramatically with the development of tyrosine kinase inhibitors (TKIs) that target sensitizing somatic mutations of the epidermal growth factor receptor (EGFR). Despite remarkable initial responses, patients eventually develop progressive disease, with the most common cause of resistance to first-lineEGFR TKIs being the acquired T790M mutation. Various third-generationEGFR TKIs have been developed to specifically target this acquired mutation, of which osimertinib is currently the only approved agent. In addition, the eagerly anticipated data from the FLAURA study recently found improved efficacy with increased progression-free survival (PFS) with osimertinib compared to standard of care first-generationEGFR TKIs in the first-line setting. Of note, osimertinib has also demonstrated promising efficacy in patients with known brain metastases. However, as patients invariably develop resistance during treatment with osimertinib, most commonly with the development of triple mutatedEGFR (sensitizing mutations/T790M/C797S), which is resistant to all existingEGFR TKIs, efforts are currently ongoing to develop new strategies or novel compounds to specifically target this resistance mechanism.
Source: Targeted Oncology - Category: Cancer & Oncology Source Type: research

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Immunotherapy,Volume 10, Issue 5, Page 403-410, April 2018.
Source: Immunotherapy - Category: Allergy & Immunology Authors: Source Type: research
Abstract Epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have markedly improved the response of non-small cell lung cancer (NSCLC) with EGFR-mutant patients. However, these patients inevitably come cross acquired resistance to EGFR-TKIs. The transformation of lung adenocarcinoma to small cell lung cancer (SCLC) following treatment with EGFR-TKIs is rare, which leads to resistance to EGFR-TKIs. The present case concerns a case of a 38-year-old man presenting with cough and dyspnea. Radical resection was performed and confirmed an EGFR exon 21 L858R lung adenocarcinoma. However, the patient ...
Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Tags: Cancer Biol Ther Source Type: research
ConclusionsYoung patients are associated with an increased likelihood of gene mutations and can receive a better prognosis when patients harboring gene mutations are treated with EGFR-TKIs or ALK inhibitors.
Source: Clinical and Translational Oncology - Category: Cancer & Oncology Source Type: research
Conclusions Synchronous solitary M1 treated with chemotherapy and operation at both sites resulted in better survival. Survival of NSCLC with synchronous solitary M1 was more similar to stage III than other stage IV NSCLCs. The eighth TNM classification takes this into account by distinguishing between stages M1b and M1c.
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
Authors: Sun YW, Xu J, Zhou J, Liu WJ Abstract Brain metastases are very common in lung cancer patients. The condition of these patients is complicated and difficult to treat, and adverse reactions following treatment can affect the nervous system, which severely reduces quality of life. Lung cancers are categorized as small cell lung cancers and non-small cell lung cancers. Patients with brain metastasis of small cell lung cancers are generally treated with brain radiotherapy and systemic chemotherapy, but stage III/IV patients with brain metastasis of non-small cell lung cancers are generally not responsive to ra...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
In conclusion, our findings suggest that AZD3759 combined with radiation enhances the antitumor activity in BM from EGFRm NSCLC, this combination therapy may be an effective treatment option for BM from EGFRm NSCLC. This article is protected by copyright. All rights reserved.
Source: International Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Article Source Type: research
Abstract INTRODUCTION: Several reports attest the feasibility and the favorable outcomes of kinase inhibitors administration through feeding tubes or percutaneous endoscopic gastrostomies (PEG), mainly in non-small cell lung cancer (NSCLC) patients exposed to first-generation compounds. Here we present the case of an ALK-positive NSCLC patient who achieved cerebral and extra-cranial disease response with ceritinib (a novel ALK inhibitor) administered through a nasogastric tube (NGT). We moreover provide a review gathering clinical successes obtained with targeted agents intake through NGT or PEG. CASE PRESENT...
Source: Current Drug Targets - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Targets Source Type: research
The recently published QUARTZ study [1,2] showed that the routine use of whole brain radiotherapy (WBRT) in patients with brain metastases from non-small cell lung cancer did not confer a survival benefit or an improvement in quality of life compared with best supportive care only. There was, however, a suggestion that certain groups of patients may still derive a benefit from WBRT with an improved survival in those aged under 60 years and a non-significant improvement in those with a good performance status.
Source: Clinical Oncology - Category: Radiology Authors: Tags: Letter Source Type: research
Purpose of review The review will highlight recent advances in development of ALK-TKIs and management of patients with ALK-positive nonsmall cell lung cancer. Recent findings There has been rapid progress in the use of targeted therapies for ALK-positive NSCLC. Since the discovery, development and approval of crizotinib in 2011, three second-generation ALK-TKIs, ceritinib, alectinib and brigatinib have been approved by the FDA. A range of newer generation ALK inhibitors with improved potency against ALK and against mutations that confer resistance to crizotinib are in clinical development. Summary Our review will d...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: LUNG AND MEDIASTINUM: Edited by Robert Pirker Source Type: research
Authors: Lee SY, Kang EJ, Lee SY, Kim HJ, Min KH, Hur GY, Shim JJ, Kang KH, Oh SC, Seo JH, Kim JS Abstract The present study investigated the importance of comorbidity scores and clinical parameters in elderly patients with non-small cell lung cancer (NSCLC) not harboring epidermal growth factor receptor (EGFR) mutations who received second-line chemotherapy. The present study also compared the efficacy of tyrosine kinase inhibitor and cytotoxic chemotherapy as second-line treatment in elderly patients. The present study retrospectively reviewed the treatment of elderly patients with NSCLC (≥70 years old) who re...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
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