Genetic Fusion Detection May Benefit NSCLC Patients

A case study from the University of Colorado suggests that traditional gene testing for NSCLC patients may not be sufficient for detecting potential oncogenic drivers.

A new report is highlighting the importance of broad molecular testing for non–small-cell lung cancer (NSCLC) and the importance of good transparency from commercial laboratories on what their assays covered. In a case study published in JCO Precision Oncology, researchers report on the discovery of a novel fusion gene that involves MET in a tumor sample from a patient with NSCLC who was negative for other known oncogenic drivers. Surprisingly, the patient demonstrated a dramatic response to off-label treatment with crizotinib, which is a small-molecule tyrosine kinase inhibitor with activity against hepatocyte growth factor receptor.

The authors theorized that the MET fusion gene product was an oncogenic driver in the patient’s tumor. However, it would not have been detected with traditional gene testing. They contend that it is now imperative to identify the driver oncogene status of NSCLC patients. Until recently, it was possible to test for a small number of genes. However, the recent rapid expansion in the number of characterized driver oncogenes has changed the landscape.

The authors write that the increase in the number of approved therapies and the large number of clinical studies testing drugs that target novel oncogenes has changed the role of the oncologist. It now calls for clinicians to consider the evaluation of multiple genes simultaneously. In this study, researchers examined the tumor sample from a late-stage lung cancer patient using an assay that detects gene fusions in dozens of genes.

Terry L. Ng, MD, a senior fellow in clinical and translational research in thoracic oncology at the University of Colorado Cancer Center in Aurora, said clinicians need to think about which assays they currently are ordering. He said the treatment paradigm is changing in 2017 and oncologists need to start thinking about broader molecular profiling in NSCLC patients. He also noted that in some respects it is a new era when it comes to managing patients with NSCLC.

“I think it is a big advance in that it tells us we need to look broader and deeper. We are now applying better technologies and techniques,” Ng said in an interview with OncoTherapy Network.

Ng and colleagues used a relatively new assay called Archer FusionPlex, which was developed by the Boulder-based biotechnology company ArcherDX. Instead of testing for alterations in individual genes, the test explores an entire class of genetic changes, testing simultaneously for gene fusions in 53 cancer-related genes.

Robert C. Doebele, MD, PhD, an associate professor of medical oncology at the University of Colorado School of Medicine, said this case highlights a number of changes that are occurring in the management of NSCLC patients. “I think if this association holds up in additional datasets, this has the potential to accelerate development of new drugs or new drug combinations, as it may give an early signal in clinical trials whether a new drug or combination may be superior to existing therapies,” he told OncoTherapy Network.