Profile of the Roche cobas® EGFR mutation test v2 for non-small cell lung cancer

Abstract

The discovery of driver mutations in non-small cell lung cancer (NSCLC) has led to the development of genome-based personalized medicine. Fifteen to 20% of adenocarcinomas harbor an epidermal growth factor receptor (EGFR) activating mutation associated with responses to EGFR tyrosine kinase inhibitors (TKIs). Individual laboratories' expertise and the availability of appropriate equipment are valuable assets in predictive molecular pathology, although the choice of methods should be determined by the nature of the samples to be tested and whether the detection of only well-characterized EGFR mutations or rather, of all detectable mutations, is required. Areas covered: The EGFR mutation testing landscape is manifold and includes both screening and targeted methods, each with their own pros and cons. Here we review one of these companion tests, the Roche cobas® EGFR mutation test v2, from a methodological point of view, also exploring its liquid-biopsy applications. Expert commentary: The Roche cobas® EGFR mutation test v2, based on real time RT-PCR, is a reliable option for testing EGFR mutations in clinical practice, either using tissue-derived DNA or plasma-derived cfDNA. This application will be valuable for laboratories with whose purpose is purely diagnostic and lacking high-throughput technologies.

Clinical relevance of circulating tumor DNA assessed through deep sequencing in patients with metastatic colorectal cancer

“…Although ctDNA are cleared from the blood by the liver and kidney, its half‐lives range from 15 minutes to several hours, suggesting that it could be a real‐time biomarker for assessment of quality (tumor genotype) and quantity (tumor burden) of the cancer . Recently, Food and Drug Administration approved epidermal growth factor receptor ( EGFR ) mutation test using plasma as a diagnostic tool for the detection of EGFR mutations to predict the erlotinib (EGFR tyrosine kinase inhibitor) response in patients with non‐small‐cell lung cancer . Thus, ctDNA monitoring could be useful biomarker for tumor recurrence, drug resistance, and treatment response, which enable physicians to select more appropriate treatment to each patient …”

Cost-Consequence Analysis of Three Different Diagnostic Strategies in the First- and Second-Line Treatment of Locally Advanced or Metastatic Non-Small-Cell Lung Cancer

“…It is estimated that 85% of these patients are eligible for the tissue biopsy [2], while the remaining 15% potentially to the liquid biopsy only. Among the patients who perform the tissue biopsy, the outcome may not be determinable in 30% of cases [16]. Finally, 40% of patients with a mNSCLC diagnosis are eligible to receive the second-line treatment [3]; of them, 82% are eligible for the tissue re-biopsy [5] and 100% for the liquid one.…”

Personalized medicine: biomarkers and companion diagnostics

“…In addition, liquid biopsy -already validated in many clinical trials -is a non-invasive, reproducible method, also obtainable from patients with severe morbidity. In this regard, the results of a recent study with osimertinib -an inhibitor of EGFR T790M mutation-related tyrosine kinases -support the use of the COBAS ® test to detect EGFR mutations through plasma samples [4]. One of the many advantages of this test (as however is also the case of other CDx) is the swiftness of its execution.…”

“…In addition, it has been noticed that, in such tests, in 12.2% of cases the mutational status still could not be assessed [4]. The analysis of the DNA derived from plasma can then be an important alternative even when, under certain conditions, the use of tissue is unfeasible, or too risky.…”

“…EGFR mutation testing for the selection of treatments in NSCLC patients were developed following the introduction of first-and second-generation EGFR TKIs. Despite the fact that the analysis of the tissue biomarkers still represents the gold standard, it should be noted, however, that up to 30% of the patients with advanced NSCLC cannot benefit from it, due to a lack of suitable tissue [4]. In particular, with third-generation EGFR TKIs (osimertinib), it's not always possible to execute the Exon 20 T790M mutation test using tissue samples; in this case, liquid biopsies are a great opportunity.…”