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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Lung cancer is the most common cancer worldwide, both in new cases and deaths (Ferlay et al., 2012). Non-small cell lung carcinomas (NSCLC) account for approximately 60% of all lung cancers and tend to progress in a slower fashion compared to small cell lung carcinomas (SCLC) (approximately 12% of lung cancers) a more aggressive type of lung cancer, known to metastasise to the brain (Kumar et al., 2013). There are several treatment options to be considered for lung cancer patients and they are: surgery (e.g.
Source: Critical Reviews in Oncology Hematology - Category: Cancer & Oncology Authors: Source Type: research
Authors: Abdallah SM, Wong A Abstract Significant progress has been made in the treatment of stage iv non-small-cell lung cancer (nsclc); however, the prognosis of patients with brain metastases remains poor. Resection and radiation therapy remain standard options. This issue is an important one because 10% of patients with nsclc have brain metastases at diagnosis, and 25%-40% develop brain metastases during their disease. Standard chemotherapy does not cross the blood-brain barrier. However, there is new hope that tyrosine kinase inhibitors (tkis) used in patients with identified targetable mutations such as mutat...
Source: Current Oncology - Category: Cancer & Oncology Tags: Curr Oncol Source Type: research
Authors: Alshangiti A, Chandhoke G, Ellis PM Abstract Angiogenesis is frequent in non-small-cell lung cancer (nsclc) and is associated with more aggressive disease. Many clinical trials have evaluated the addition of antiangiogenic therapy to standard therapies for patients with nsclc. Bevacizumab, a monoclonal antibody directed against serum vascular endothelial growth factor, in combination with carboplatin-paclitaxel chemotherapy, has been shown to improve survival for patients with nsclc. However, bevacizumab-based therapy is not suitable for many nsclc patients, including those with squamous histology, poor pe...
Source: Current Oncology - Category: Cancer & Oncology Tags: Curr Oncol Source Type: research
AbstractThe identification of anaplastic lymphoma kinase rearrangements in 2 –5% of patients with non-small-cell lung cancer led to rapid advances in the clinical development of oral tyrosine kinase inhibitors. Anaplastic lymphoma kinase inhibitors are an effective treatment in preclinical models and patients with anaplastic lymphoma kinase-translocated cancers. Four anapl astic lymphoma kinase inhibitors (crizotinib, ceritinib, alectinib, and brigatinib) have recently been approved. Post-marketing studies provided additional pharmacokinetic information on their pharmacokinetic parameters. The pharmacokinetic propert...
Source: Clinical Pharmacokinetics - Category: Drugs & Pharmacology Source Type: research
Conclusion: While no single variant was associated with brain metastasis, this study describes a potential gene panel for the identification of patients at risk and implicates PI3K/AKT signaling as a therapeutic target. PMID: 29899834 [PubMed]
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Conclusion: Smoking history, extracranial metastases, and neurosurgical resection were considered independent negative prognostic factors for OS. These findings may facilitate pretreatment prediction of survival and can be used for selecting patients for more appropriate treatment options.
Source: Journal of Cancer Research and Therapeutics - Category: Cancer & Oncology Authors: Source Type: research
Non-small cell lung carcinoma (NSCLC) has the highest incidence of metastases to the central nervous system amongst all solid tumours [1]. Detection of synchronous brain metastasis in lung cancer can have significant impact on treatment strategy. Whether all patients presenting with NSCLC should undergo routine brain imaging during staging has long been a matter of debate, with no clear consensus [2 –6]. The reported low prevalence of metastases in the absence of neurological symptoms [2,7,8] provides the rationale for limiting head imaging to either patients with abnormal neurological findings, or to those with more...
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
Conclusions: Afatinib may be the optimal EGFR-TKI for advanced lung adenocarcinoma harboring EGFR-activating mutations, particularly in the absence of BM. Patients with exon 19 deletions taking afatinib had potentially long PFS. An afatinib dose of 30 and 40 mg has similar effect. Methods: We conducted this retrospective study at a single medical center from January 2013 to March 2017 and used PFS to evaluate the effectiveness of gefitinib, erlotinib, and afatinib in patients with advanced lung adenocarcinoma harboring EGFR mutations. PMID: 29849936 [PubMed]
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
We described the treatment rationale and procedure for a phase II study of docetaxel plus ramucirumab for non–small cell lung cancer (NSCLC) patients with brain metastasis (RAMNITA study: University Information Network Clinical Trials Registry identification no. [UMIN]: 000024551). Combination therapy of angiogenetic inhibitor with chemotherapy improved the outcome of patients with brain metastasis in previous reports; however, the efficacy of ramucirumab, a vascular endothelial growth factor receptor-2 monoclonal antibody, for brain metastasis has not been shown. Patients and methods: This RAMNITA study is a pros...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Study Protocol Clinical Trial Source Type: research
Brain metastases (BM) are diagnosed in approximately 40% of non-small cell lung cancer (NSCLC) patients during the course of their disease [1]. They are a poor prognostic factor and can have a negative impact on quality of life (QoL) [2 –4]. Depending on symptoms, number, size and locations of the BM, patients can be treated locally with stereotactic radiotherapy (SRT), surgery or whole brain radiation (WBRT) [5]. In those with neurologically asymptomatic BM another option is upfront systemic treatment (targeted treatment or chem otherapy) [5,6].
Source: Cancer Treatment Reviews - Category: Cancer & Oncology Authors: Tags: Anti-Tumour Treatment Source Type: research
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