Biodesix®’ VeriStrat® Test Identifies T790M-Mutated Advanced Non-Small Cell Lung Cancer Patients Who Are More Likely to Have Improved Progression-Free Survival on Third Generation EGFR-TKI Therapy

Excerpt:

“Combined results from subset analyses of the TIGER-X and TIGER-2 clinical trials show that the VeriStrat test stratifies T790M-mutated patients with previously-treated, advanced non-small cell lung cancer (NSCLC) who are more or less likely to experience longer progression-free survival (PFS) when treated with a third-generation EGFR-TKI therapy. Clinical trial data suggesting the test’s potential for identifying better candidates for third-generation EGFR-TKI therapy were presented in Chicago last Friday at the at the IASLC Multidisciplinary Symposium in Thoracic Oncology hosted by the International Association for the Study of Lung Cancer.”

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AZD9291 Shows Clinical Activity in Non-Small Cell Lung Cancer Patients with Leptomeningeal Disease

“The epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) AZD9291 crossed the blood-brain barrier and showed clinical activity in heavily pretreated non-small cell lung cancer (NSCLC) patients with leptomeningeal disease, a disease in which lung cancer cells spread to the membranes surrounding the brain and spinal cord, according to data from a phase I BLOOM clinical trial presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Nov. 5–9.

” ‘Leptomeningeal disease at initial diagnosis of NSCLC is rare; however, as their lung cancer progresses, up to 15 percent of patients will develop this devastating complication. Additionally, an increased risk of central nervous system [CNS] involvement has been reported among patients with EGFR-mutant NSCLC, in particular those treated with a first-generation EGFR-TKI,’ said Dae Ho Lee, MD, PhD, associate professor in the Department of Oncology in the University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.”


New EGFR Inhibitor AZD9291 Shows Promising Activity in Treatment-Resistant Non–Small Cell Lung Cancer

“Findings from a phase I study of a new mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, AZD9291, point to a promising new treatment option for patients with advanced, EGFR-mutant, non–small cell lung cancer (NSCLC) that is resistant to standard EGFR inhibitors. Roughly 50% of patients experienced tumor shrinkage, and the drug worked particularly well in patients with the T790M mutation (detected in 60% of patients), which causes the most common form of EGFR therapy resistance. The study was presented at a presscast in advance of the 2014 ASCO Annual Meeting (Abstract 8009^).”

Editor’s note: This story is about a new targeted therapy drug called AZD9291 that is designed to attack tumors with a mutation in the EGFR gene, as detected by molecular testing. In particular, it is designed for patients who are resistant to other so-called EGFR inhibitors as a result of developing a particular EGFR mutation known as T790M. In a clinical trial to test the drug in patients, it was found to show promising results for patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations, and even better results in patients with the T790M mutation.


Chemotherapy May be Preferable Option in NSCLC with Wild Type EGFR

“Chemotherapy yielded improved PFS vs. treatment using epidermal growth factor receptor tyrosine kinase inhibitors in patients with advanced non–small cell lung cancer with wild-type epidermal growth factor receptor.

“However, researchers noted that chemotherapy did not confer a benefit over EGFR TKIs in terms of OS.

“In the meta-analysis, researchers conducted a literature search of several scientific databases, including PubMed, Embase, Cochrane database, and abstracts from meetings of the American Society of Clinical Oncology and the European Society of Medical Oncology.”

Editor’s note: The study described here compared chemotherapy to treatment with targeted therapy drugs called EGFR TKIs for patients with non-small cell lung cancer (NSCLC) whose tumors did NOT have mutations in the EGFR gene. (EGFR mutations and other mutations are often tested to help determine patients’ treatment options.) The scientists found that chemotherapy  may be a better option for these patients. Chemotherapy seemed to extend the time that patients lived without their disease worsening. However, it did not show any benefit over EGFR TKIs in terms of overall survival.


Synergistic Effects of Metformin Treatment in Combination with Gefitinib, a Selective EGFR Tyrosine Kinase Inhibitor, in LKB1 Wild-type NSCLC Cell Lines

EGF receptor (EGFR) tyrosine kinase inhibitors (TKI) are effective against lung cancer, but clinical resistance to these agents has developed. Metformin is a widely used antidiabetic drug and also displays significant growth-inhibitory and proapoptotic effects in several cancer models, alone or in combination with chemotherapeutic drugs.

Metformin and gefitinib are synergistic in LKB1 wild-type NSCLC cells. However, further studies are required to investigate better the effect of metformin action on the RAS/RAF/MAPK pathway and the best context in which to use metformin in combination with molecular targeted agents.


USP8 Is a Novel Target for Overcoming Gefitinib Resistance in Lung Cancer

Common treatment modalities for non–small cell lung cancer (NSCLC) involve the EGF receptor-tyrosine kinase inhibitors (EGFR-TKIs) like gefitinib and erlotinib. However, the vast majority of treated patients acquire resistance to EGFR-TKIs, due, in large part, to secondary mutations in EGFR or amplification of the MET gene. Our purpose was to test ubiquitin-specific peptidase 8 (USP8) as a potential therapeutic target for gefitinib-resistant and -sensitive non–small cell lung cancer (NSCLC).

Our results show for the first time that the inhibition of USP8 activity or reduction in USP8 expression can selectively kill NSCLC cells. We propose USP8 as a potential therapeutic target for gefitinib-resistant and -sensitive NSCLC cells.


KRAS Mutation as the Biomarker of Response to Chemotherapy and EGFR-TKIs in Patients With Advanced Non-Small Cell Lung Cancer: Clues For Its Potential Use in Second-Line Therapy Decision Making

In patients with non-small cell lung cancer (NSCLC), knowledge of the epidermal growth factor receptor (EGFR) mutation status is fundamental for selecting the treatment involving EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Little information is available regarding the response and progression-free survival (PFS) in platinum-based chemotherapy (CT) versus EGFR-TKIs in the presence or absence of KRAS mutation, particularly in patients without EGFR mutation…”