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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Conclusion: SIB-IMRT with the dose/fractionation based on the fusion imaging of MRI-CT is feasible and safe. It is beneficial to the NSCLC patients with BM and can reduce the overall costs of treatment.
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
CONCLUSIONSThis expanded and updated analysis confirms that single-fraction preoperative SRS confers excellent cavity local control with very low risk of RN or LMD. Preoperative SRS has several potential advantages compared to postoperative SRS, including reduced risk of RN due to smaller irradiated volume without need for cavity margin expansion and reduced risk of LMD due to sterilization of tumor cells prior to spillage at the time of surgery. Subtotal resection, though infrequent, is associated with significantly worse cavity LR and OS. Based on these results, a randomized trial of preoperative versus postoperative SRS...
Source: Journal of Neurosurgery - Category: Neurosurgery Tags: J Neurosurg Source Type: research
Xiao-Jing Du, Su-Ming Pan, Shu-Zhen Lai, Xiao-Nan Xu, Mei-Ling Deng, Xiao-Hui Wang, Dun-Chen Yao, Shao-Xiong Wu
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Lung cancer is the leading cause of cancer-related mortality in both men and women. Non-small cell lung cancer (NSCLC) accounts for 85-90% of all lung cancer incidence [6] and also represents the most common cause of cerebral metastasis either at diagnosis or at relapse/progression [7]. Approximately 10-20% of NSCLC patients will have brain metastasis at initial presentation [8,9]. Another 25-50% will develop brain metastases during the course of their disease [10]. Among NSCLC histological subtypes, non-squamous carcinomas carry a greater risk for extra-thoracic metastasis compared to squamous cell histologies [11].
Source: Lung Cancer - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
d-Mende Michael Meister A major part of non-small cell lung cancer (NSCLC) patients treated with mono- or multimodal concept develop therapy resistance. Despite the abundance of biomarkers investigated in the past, there is still a need for valid NSCLC biomarkers. Glycodelin, an immunosuppressive endometrial protein, has been shown to be also expressed in NSCLC. Here, we investigated its potential as a biomarker in metastatic and advanced stage NSCLC. Glycodelin gene and protein expression were measured in 28 therapy-naïve resected tumors as well as in corresponding brain (n = 16) and adrenal gland (n = 12) ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Afatinib is an oral irreversible epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI) indicated in first-line treatment of advanced EGFR-mutant (EGFRm+) non-small cell lung cancer (NSCLC). D...
Source: BMC Cancer - Category: Cancer & Oncology Authors: Tags: Research article Source Type: research
Background: Several studies have confirmed the important role of the gut microbiota in the regulation of immune functions and its correlation with different diseases, including cancer. While brain-gut and liver-gut axes have already been demonstrated, the existence of a lung-gut axis has been suggested more recently, with the idea that changes in the gut microbiota could affect the lung microbiota, and vice versa. Likewise, the close connection between gut microbiota and cancer of proximal sites (intestines, kidneys, liver, etc.) is already well established. However, little is known whether there is a similar relation wh...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Study Protocol Clinical Trial Source Type: research
Authors: Abstract OBJECTIVEPrevious Japanese Leksell Gamma Knife Society studies (JLGK0901) demonstrated the noninferiority of stereotactic radiosurgery (SRS) alone as the initial treatment for patients with 5-10 brain metastases (BMs) compared with those with 2-4 BMs in terms of overall survival and most secondary endpoints. The authors studied the aforementioned treatment outcomes in a subset of patients with BMs from non-small cell lung cancer (NSCLC).METHODSPatients with initially diagnosed BMs treated with SRS alone were enrolled in this prospective observational study. Major inclusion criteria were the exis...
Source: Journal of Neurosurgery - Category: Neurosurgery Tags: J Neurosurg Source Type: research
We describe recent developments in the rapidly evolving field of anaplastic lymphoma kinase-targeting agents. Recent findings Five targeted drugs are currently available in the clinic via regular approval or named patient programs, including crizotinib, ceritinib, alectinib, brigatinib and lorlatinib. Further drugs are tested in clinical trials. This review summarizes published data, together with drug-specific information on dosing and toxicity. Moreover, we discuss different clinical scenarios and potential treatment options in patients with tumor progression, based on current literature and our own experience. Summa...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: LUNG AND MEDIASTINUM: Edited by Robert Pirker Source Type: research
Although crizotinib shows marked antitumor activity in anaplastic lymphoma kinase (ALK) rearrangement-positive non-small-cell lung cancer (NSCLC) patients, all treated patients ultimately develop resistance to this drug. Isolated central nervous system failure without progression at extracranial sites is a common progression pattern in ALK rearrangement-positive NSCLC patients treated with crizotinib. Here, we report the success of crizotinib combined with whole-brain radiotherapy in an ALK rearrangement-positive NSCLC patient who developed leptomeningeal carcinomatosis and progression of multiple brain metastases. Additio...
Source: Case Reports in Oncology - Category: Cancer & Oncology Source Type: research
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