Abstract
Recent changes in lung cancer care, including new approvals in first line and the introduction of high-throughput molecular technologies in routine testing led us to question ourselves on how deeper molecular testing may be helpful for the optimal use of targeted drugs. In this article, we review recent results in the scope of personalized medicine in lung cancer. We discuss biomarkers that have a therapeutic predictive value in lung cancer with a focus on recent changes and on the clinical value of large scale sequencing strategies. We review the use of second- and third-generation EGFR and ALK inhibitors with a focus on secondary resistance alterations. We discuss anti-BRAF and anti-MEK combo, emerging biomarkers as NRG1 and NTRKs fusions and immunotherapy. Finally, we discuss the different technical issues of comprehensive molecular profiling and show how large screenings might refine the prediction value of individual markers. Based on a review of recent publications (2012–2018), we address promising approaches for the treatment of patients with lung cancers and the technical challenges associated with the identification of new predictive markers.
Highlights
Lung cancer remains the most common cause of cancer deaths worldwide with more than a million deaths per year [1]
progression free survival (PFS) are often longer in patients with ROS1 rearranged tumors as compared to anaplastic lymphoma kinase (ALK) and only a few mutations were described in ROS1 tyrosine kinase domain as mechanism of crizotinib resistance
Many reviews have discussed the clinical value of molecular alterations in lung cancer
Summary
Lung cancer remains the most common cause of cancer deaths worldwide with more than a million deaths per year [1]. Phenotypic alterations, EMT and the acquisition of stem cell features are consistent mechanisms of resistance to all EGFR-TKIs. The FLAURA study [51] is a phase III clinical trial which compared osimertinib to first-generation EGFR-TKI in first line treatment of EGFR mutated NSCLC. There are two situations were MET testing could help treatment decision: patients with a non-KRAS, BRAF, EGFR, or HER2 tumor for which the identification MET as a driver could lead to specific treatment and patients with EGFR mutated tumors secondary resistance In these two situations, MET inhibitors have been tested in combination with EGFR TKIs: in a randomized EGFR wild type cohort of 111 patients, PFS was significantly improved in the cabozantinib group (4.3 months), erlotinib plus cabozantinib group (4.7 months) compared with erlotinib alone (1.8 months) [63]. Different results suggest that smoking status may be a predictive marker for survival benefits to immunotherapy, possibly due to the existence of a high mutation load in tumors from smokers
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