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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Abstract PURPOSE: Patients with epidermal growth factor receptor (EGFR) mutation-positive (EGFRm) non-small-cell lung cancer commonly experience disease progression in the CNS. Here, we assess the impact of CNS disease on resource utilization and outcomes in patients who are EGFRm. METHODS: We completed a retrospective review of all advanced patients who were EGFRm, referred to BC Cancer, and treated with a first- and/or second-generation EGFR tyrosine kinase inhibitor from 2010 to 2015. Baseline characteristics, systemic treatment, and CNS management were collected. We compared health resource utilization (H...
Source: JOP - Category: Gastroenterology Authors: Tags: J Oncol Pract Source Type: research
CONCLUSIONS: In NSCLC the use of PET/MRI, including a dedicated pulmonary MR imaging protocol, provides a comparable diagnostic value for determination of tumor resectability compared to PET/CT. Advances in knowledge: Our findings suggest that whole body PET/MRI can safely be used for the local staging of NSCLC patients. Further studies are warranted to determine whether it is feasible to integrate an imaging sequence in a whole body PET/MRI setting with the potential advantage of detection of liver or brain metastases. PMID: 30209954 [PubMed - as supplied by publisher]
Source: The British Journal of Radiology - Category: Radiology Authors: Tags: Br J Radiol Source Type: research
This article summarizes the latest clinical trials concerning the use of radiotherapy, chemotherapy, molecularly targeted therapies and immunotherapy in lung cancer patients, with particular consideration of brain lung cancer metastasis prevention. The literature search was undertaken via PubMed and EMBASE searches and relevant articles are included in this review. Expert Commentary: The recent data supports that EGFR-TKIs and ALK inhibitors are clinically relevant for first-line treatment to prevent and treat CNS metastases in molecularly-selected NSCLC patients. In the future, high hopes for the prevention of CNS metasta...
Source: Expert Review of Anticancer Therapy - Category: Cancer & Oncology Tags: Expert Rev Anticancer Ther Source Type: research
ConclusionsThe developed model to describe resistance suggests that the resistance to EGFR-inhibition seen in these xenografts is best described by assuming a small percentage of cells are resistant to treatment at baseline. This model suggests changes to dosing and dosing schedule may not prevent resistance to treatment developing, and that additional treatments would need to be used in combination to overcome resistance.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
Conclusions: In very lethal non-small cell lung cancer subtypes such as the sarcomatoid variants, high tumor burden and deteriorated general conditions should not preclude, at least in some cases, the use of immunotherapy. Anti-PD1 may also have a reliable role in disease control in the brain. Lastly, the strong rationale behind sarcomatoid histology should further prompt trials exploring immunotherapeutic approaches in this subset of non-small cell lung cancer.Case Rep Oncol 2018;11:615 –621
Source: Case Reports in Oncology - Category: Cancer & Oncology Source Type: research
Gokoulakrichenane Loganadane, Fr édéric Dhermain, Guillaume Louvel, Paul Kauv, Eric Deutsch, Cécile Le Péchoux, Antonin Levy
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
The optimal approach to follow patients up after surgical resection of non-small cell lung cancer (NSCLC) is keenly debated; including what imaging modality to use and the intensity of clinical assessments. A systematic review in 2012 concluded that “the paucity of evidence precludes firm evidence based guidelines” [1]. This uncertainty leads to a variability of practice nationally and internationally, which ranges from routine physical examination plus chest X-ray (CXR) [2] to more intensive protocols including routine computed tomography (CT) of the thorax, bronchoscopy, abdominal ultrasound, CT brain and bon...
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
As one of the most common malignant tumors, lung cancer is a leading cause of cancer-related mortality in China and worldwide [1]. Non-small cell lung cancer (NSCLC) accounts for 85% of primary lung cancers [2], 25-40% of which develop brain metastases (BM) [3,4]. In the past, survival after the occurrence of BM was poor, and treatment was often considered futile [5,6]. With the recent advent of molecular targeted therapies, prolonged survival has been achieved in patients with BM and gene alterations [7 –10], benefiting from EGFR TKIs such as icotinib [11], erlotinib [12] and Osimertinib [13], as well as ALK TKIs su...
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
Conclusions: Exact incidence of T790M mutations after progression on TKI s in Asian population is not exactly known and requires large data, as incidence may be different than reported in the Western population. Rebiopsy and ddPCR help to determine the most common type of resistance after progression on TKI, for which effective targeted therapy is available.
Source: Lung India - Category: Respiratory Medicine Authors: Source Type: research
Authors: Schoenmaekers JJAO, Dingemans AC, Hendriks LEL PMID: 30123551 [PubMed]
Source: Journal of Thoracic Disease - Category: Respiratory Medicine Tags: J Thorac Dis Source Type: research
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