Large-scale screening for somatic mutations in lung cancer

Lung cancer is the leading cause of cancer-related death worldwide. More than 85% of cases are classified as non-small-cell lung cancer (NSCLC), with predicted 5-year survival of 16%. However, technological advances in the past decade, including the introduction of next-generation sequencing, have allowed for identification of several genetic mutations. 1 Chen Z Fillmore CM Hammerman PS et al. Non-small-cell lung cancers: a heterogeneous set of diseases. Nat Rev Cancer. 2014; 14: 535-546 Crossref PubMed Scopus (1067) Google Scholar These mutations are considered to be actionable oncogenic drivers (ie, treatable with specific drugs) since they cause specific subclasses of NSCLC, and therefore can be targeted with selective inhibitors. One example is NSCLC harbouring mutations in the epidermal growth factor receptor (EGFR) gene, mainly associated with lung adenocarcinoma. In view of these advances, chemotherapy can no longer be regarded as the standard treatment for all patients, but rather the default treatment for those without oncogenic driver mutations. 2 Rosell R Carcereny E Gervais R et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012; 13: 239-246 Summary Full Text Full Text PDF PubMed Scopus (4429) Google Scholar In an unprecedented endeavour reported in The Lancet, the French National Cancer Institute (INCa), together with the French Cooperative Thoracic Intergroup (IFCT), have reported on a 1-year nationwide programme assessing testing for EGFR, HER2 (also known as ERBB2), KRAS, BRAF, and PIK3CA mutations, as well as ALK rearrangements in NSCLC, with the aim of selecting genotype-directed therapy and studying associations with survival. 3 Barlesi F Mazieres J Merlio J-P et al. for the Biomarkers France contributorsRoutine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet. 2016; (published online Jan 14.)http://dx.doi.org/10.1016/S0140-6736(16)00004-0 Summary Full Text Full Text PDF Scopus (688) Google Scholar This work, by Fabrice Barlesi and colleagues, builds on earlier studies which established actionable oncogenic mutations in NSCLC. Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT)Routine nationwide molecular profiling of patients with advanced NSCLC is feasible. The frequency of genetic alterations, acceptable turnaround times in obtaining analysis results, and the clinical advantage provided by detection of a genetic alteration suggest that this policy provides a clinical benefit. Full-Text PDF