The development of biomarker-driven targeted therapy has resulted in substantial benefits for patients with non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations, and rearrangements involving the anaplastic lymphoma kinase (ALK) gene or the ROS1 gene. For patients with EGFR-mutant NSCLC EGFR tyrosine kinase inhibitors (eg, gefitinib, erlotinib, and afatinib) have a superior objective response rate and progression-free survival compared with chemotherapy in the first-line setting.1-3 For patients who have disease progression on EGFR tyrosine kinase inhibitor and with NSCLC with an EGFR T790M mutation osimertinib has demonstrated a superior response rate and progression-free survival compared with chemotherapy in the second-line setting.4 For patients with ALK rearrangements ALK tyrosine kinase inhibitors (eg, crizotinib, ceritinib) have a superior response rate and progression-free survival compared with chemotherapy in the first-line setting, and for patients who experience disease progression, ceritinib and alectinib have demonstrated clinically relevant response rates and progression-free survival.5-9 For patients with ROS1 rearrangements, targeted therapy, is associated with a higher response rate and longer progression-free survival than has been observed with chemotherapy. These molecular alterations are more common in NSCLC with adenocarcinoma histology and in the minority of patients with a light smoking or never smoking history. The success of these targeted therapies in molecularly defined subsets of NSCLC made the development of targeted therapies and identification of predictive biomarkers a focus of thoracic oncology research. Routine molecular testing is now the standard of care for patients with NSCLC with adenocarcinoma histology.10,11
Kaufman J, Stinchcombe TE. Treatment of KRAS-Mutant Non–Small Cell Lung Cancer: The End of the Beginning for Targeted Therapies. JAMA. 2017;317(18):1835–1837. doi:10.1001/jama.2017.3436
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