Therapy for Stage IV Non–Small-Cell Lung Cancer Without Driver Alterations: ASCO and OH (CCO) Joint Guideline Update

All patients with nonsquamous NSCLC should have the results of testing for potentially targetable mutations (alterations) before implementing therapy for advanced lung cancer, regardless of smoking status recommendations, when possible, following other existing high-quality testing guidelines. Most patients should receive targeted therapy for these alterations: Targeted therapies against <i>ROS</i>-1 fusions, <i>BRAF</i> V600e mutations, <i>RET</i> fusions, <i>MET</i> exon 14 skipping mutations, and <i>NTRK</i> fusions should be offered to patients, either as initial or second-line therapy when not given in the first-line setting. New or revised recommendations include the following: Osimertinib is the optimal first-line treatment for patients with activating epidermal growth factor receptor mutations (exon 19 deletion, exon 21 L858R, and exon 20 T790M); alectinib or brigatinib is the optimal first-line treatment for patients with anaplastic lymphoma kinase fusions. For the first time, to our knowledge, the guideline includes recommendations regarding <i>RET, MET, and NTRK</i> alterations. Chemotherapy is still an option at most stages.Additional information is available at www.asco.org/thoracic-cancer-guidelines.