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Matthew A. Gubens and Marianne Davies

For the use of immunotherapy in metastatic non–small cell lung cancer (NSCLC), the NCCN Guidelines for NSCLC reflect the importance of assessing levels of PD-L1 expression to determine the best use of PD-1/PD-L1 inhibitors, whether alone or in combination with chemotherapy. Patients who lack a driver mutation and have tumor PD-L1 expression ≥50% are recommended to receive single-agent pembrolizumab, although combining with carboplatin/pemetrexed is also a reasonable choice, especially if there is higher burden of disease. For tumors with PD-L1 expression <50%, it is important to distinguish between nonsquamous and squamous cell carcinoma (SCC). For patients with non-SCC disease, pembrolizumab + carboplatin/pemetrexed is preferred. Alternately, a 4-drug regimen of carboplatin/paclitaxel/bevacizumab/atezolizumab is reasonable, especially for patients ineligible for pemetrexed. In patients with SCC, carboplatin + paclitaxel or nab-paclitaxel with pembrolizumab is a category 1 recommendation. Tumor mutational burden is emerging as a biomarker for efficacy but is not yet ready to be used in patient selection. Optimal management of the unique toxicities associated with immunotherapy, which can be more frequent with these combinations, is also critical for good outcomes.

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John A. Thompson, Bryan J. Schneider, Julie Brahmer, Stephanie Andrews, Philippe Armand, Shailender Bhatia, Lihua E. Budde, Luciano Costa, Marianne Davies, David Dunnington, Marc S. Ernstoff, Matthew Frigault, Brianna Hoffner, Christopher J. Hoimes, Mario Lacouture, Frederick Locke, Matthew Lunning, Nisha A. Mohindra, Jarushka Naidoo, Anthony J. Olszanski, Olalekan Oluwole, Sandip P. Patel, Sunil Reddy, Mabel Ryder, Bianca Santomasso, Scott Shofer, Jeffrey A. Sosman, Momen Wahidi, Yinghong Wang, Alyse Johnson-Chilla and Jillian L. Scavone

The aim of the NCCN Guidelines for Management of Immunotherapy-Related Toxicities is to provide guidance on the management of immune-related adverse events resulting from cancer immunotherapy. The NCCN Management of Immunotherapy-Related Toxicities Panel is an interdisciplinary group of representatives from NCCN Member Institutions and ASCO, consisting of medical and hematologic oncologists with expertise in a wide array of disease sites, and experts from the fields of dermatology, gastroenterology, neuro-oncology, nephrology, emergency medicine, cardiology, oncology nursing, and patient advocacy. Several panel representatives are members of the Society for Immunotherapy of Cancer (SITC). The initial version of the NCCN Guidelines was designed in general alignment with recommendations published by ASCO and SITC. The content featured in this issue is an excerpt of the recommendations for managing toxicity related to immune checkpoint blockade and a review of existing evidence. For the full version of the NCCN Guidelines, including recommendations for managing toxicities related to chimeric antigen receptor T-cell therapy, visit