Foundation Medicine, Inc. has announced new data demonstrating the role of MET exon 14 (METex14) alterations as drivers of growth of non-small cell lung cancer (NSCLS), resulting in the identification of a unique subset of patients likely to benefit from certain MET inhibitor targeted therapies. Strikingly, the analysis showed that the MET exon 14 alterations occurred in more than 3% of non-small cell lung cancers and identified NSCLC patients who derived meaningful clinical benefit from treatment with MET targeted therapies. Identification of this patient population by comprehensive genomic profiling with FoundationOne® is an important step towards making targeted therapy available for a wider range of patients with NSCLC. Further, the addition of METex14 alterations to the growing list of oncogenic drivers in NSCLC supports the need for broad reimbursement coverage of comprehensive genomic profiling to allow a full understanding of the genomic drivers of a patient's tumor and the matched targeted therapeutic approaches to drive improved outcomes.
"Due to the diversity of METex14 alterations, many of these alterations can only be detected in the clinical setting using comprehensive genomic profiling methods such as FoundationOne," said Ignatius Ou, M.D., Ph.D., health science associate clinical professor, University of California, Irvine "METex14 alterations define a distinct and previously underappreciated molecular subtype of lung adenocarcinoma that do not occur with other known drivers of this type of cancer. By identifying METex14 as an oncogenic driver across multiple tumor types and encouraged by convergent evidence from several groups of associated susceptibility to MET inhibitor targeted therapy, we have identified new therapeutic options for a new subpopulation of patients with this most lethal cancer."
"There is an ever-increasing body of clinical evidence demonstrating that comprehensive genomic profiling is an important, necessary step to stratify patients for appropriate targeted therapy and hence, it optimizes the opportunity for improved outcomes," said Vincent Miller, M.D., chief medical officer of Foundation Medicine. "This data, in particular, points to the significance of precision medicine. It also amplifies the critical importance of identifying patients that heretofore would likely have received cytotoxic agents that deliver only modest therapeutic response who now have the opportunity to experience significant clinical benefit based on matching the unique genomic drivers of disease with targeted therapies."
Focal amplification and activating uncommon point mutations of MET are well-characterized oncogenic drivers that confer susceptibility to targeted MET inhibitors. However, the full diversity and prevalence of recurrent somatic splice site alterations at METex14 that result in exon skipping and MET activation were previously unknown. Researchers from Foundation Medicine undertook an analysis of its information knowledgebase, FoundationCORE, to determine the frequency of MET exon 14 alterations in advanced cancers. Foundation Medicine analyzed genomic profiles from 38,048 patients who underwent comprehensive genomic profiling with FoundationOne to identify 221 patients with METex14 alterations. These alterations displayed remarkably diverse sequence composition, with 126 different genomic sequence variants represented. METex14 alterations are important recurrent alterations that are clinically and therapeutically relevant, detected most frequently in lung adenocarcinoma (3.0%), but also frequently in other lung neoplasms (2.3%), brain glioma (0.5%) and tumors of unknown primary origin (0.5%). Further in vitro studies demonstrated sensitivity to MET inhibitors in cells harboring METex14 alterations. The diversity of METex14 alterations indicates that testing via a comprehensive genomic profile like FoundationOne is necessary for detection in a clinical setting.
These data were presented in an oral presentation at the ASCO Annual Meeting titled, "Comprehensive genomic profiling of advanced cancers to identify MET exon 14 alterations that confer sensitivity to MET inhibitors" (abstract #11007), by Dr. Ou.
These data expand on previously published data in Cancer Discovery1.