Rapidly Changing Treatment Algorithms for Metastatic Nonsquamous Non-Small-Cell Lung Cancer

Background: The treatment paradigm for metastatic nonsquamous non-small-cell lung cancer (NSCLC) continues to change. Algorithms published only 6 months ago are outdated today and are dramatically different from those published a few years ago. New driver mutations continue to be identified, and the development of therapies to inhibit oncogenic addiction is ongoing. Patient survival is improving as treatments become more personalized and effective. Methods: This review looks at the outcomes of recent trials and discusses treatment options for patients with metastatic NSCLC of nonsquamous histology. Algorithms continue to change quickly, and an attempt is made to keep the paradigm current and applicable into the near future. Results: Treatment algorithms for nsclc tumours with EGFR mutations, ALK rearrangements, and ROS1 rearrangements, and for wild-type tumours are presented. A future algorithm based on new immunotherapy data is proposed. The treatment algorithm for EGFR mutation is changing with the proven efficacy of osimertinib for the acquired T790M mutation. All patients taking first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors must be tested. Conclusions: The treatment algorithm for ALK rearrangement has changed with the proven superiority of alectinib compared with crizotinib in the first-line setting. The approval of crizotinib for ROS1 rearrangements now means that patients also must be tested for that mutation. The biomarker for checkpoint inhibitors continues to be PD-L1 by immunohistochemistry stain, but whether testing will be necessary for patient selection if chemotherapy combinations are implemented will be determined soon.