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Immunotherapies for Lung Cancer

Matthew A. Gubens

In 2017, immunotherapy is the standard of care for patients with non–small cell lung cancer (NSCLC) either in the first or second line depending on programmed death ligand-1 (PD-L1) and mutation status. For first-line therapy, pembrolizumab is currently the standard of care for patients whose tumors express PD-L1 >50%. All patients with NSCLC should undergo PD-L1 testing before initiating treatment on pembrolizumab. For patients not eligible in the first line, immunotherapy is the standard of care for most in the second line. Nivolumab and atezolizumab are approved in all patients as second-line therapies after platinum-based doublet failure regardless PD-L1 expression level, although pembrolizumab is approved as second-line therapy for those whose tumors express PD-L1 >1%.

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NCCN Guidelines Updates: New Immunotherapy Strategies for Improving Outcomes in Non–Small Cell Lung Cancer

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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Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

David S. Ettinger, Douglas E. Wood, Dara L. Aisner, Wallace Akerley, Jessica Bauman, Lucian R. Chirieac, Thomas A. D'Amico, Malcolm M. DeCamp, Thomas J. Dilling, Michael Dobelbower, Robert C. Doebele, Ramaswamy Govindan, Matthew A. Gubens, Mark Hennon, Leora Horn, Ritsuko Komaki, Rudy P. Lackner, Michael Lanuti, Ticiana A. Leal, Leah J. Leisch, Rogerio Lilenbaum, Jules Lin, Billy W. Loo Jr, Renato Martins, Gregory A. Otterson, Karen Reckamp, Gregory J. Riely, Steven E. Schild, Theresa A. Shapiro, James Stevenson, Scott J. Swanson, Kurt Tauer, Stephen C. Yang, Kristina Gregory, and Miranda Hughes

This selection from the NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastatic disease. For example, new recommendations were added for atezolizumab, ceritinib, osimertinib, and pembrolizumab for the 2017 updates.

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NCCN Guidelines Insights: Non–Small Cell Lung Cancer, Version 5.2018

David S. Ettinger, Dara L. Aisner, Douglas E. Wood, Wallace Akerley, Jessica Bauman, Joe Y. Chang, Lucian R. Chirieac, Thomas A. D'Amico, Thomas J. Dilling, Michael Dobelbower, Ramaswamy Govindan, Matthew A. Gubens, Mark Hennon, Leora Horn, Rudy P. Lackner, Michael Lanuti, Ticiana A. Leal, Rogerio Lilenbaum, Jules Lin, Billy W. Loo Jr, Renato Martins, Gregory A. Otterson, Sandip P. Patel, Karen Reckamp, Gregory J. Riely, Steven E. Schild, Theresa A. Shapiro, James Stevenson, Scott J. Swanson, Kurt Tauer, Stephen C. Yang, Kristina Gregory, and Miranda Hughes

The NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the targeted therapy and immunotherapy sections in the NCCN Guidelines. For the 2018 update, a new section on biomarkers was added.

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NCCN Guidelines Insights: Small Cell Lung Cancer, Version 2.2018

Gregory P. Kalemkerian, Billy W. Loo Jr, Wallace Akerley, Albert Attia, Michael Bassetti, Yanis Boumber, Roy Decker, M. Chris Dobelbower, Afshin Dowlati, Robert J. Downey, Charles Florsheim, Apar Kishor P. Ganti, John C. Grecula, Matthew A. Gubens, Christine L. Hann, James A. Hayman, Rebecca Suk Heist, Marianna Koczywas, Robert E. Merritt, Nisha Mohindra, Julian Molina, Cesar A. Moran, Daniel Morgensztern, Saraswati Pokharel, David C. Portnoy, Deborah Rhodes, Chad Rusthoven, Jacob Sands, Rafael Santana-Davila, Charles C. Williams Jr, Karin G. Hoffmann, and Miranda Hughes

The NCCN Guidelines for Small Cell Lung Cancer (SCLC) address all aspects of disease management. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for SCLC regarding immunotherapy, systemic therapy, and radiation therapy. For the 2018 update, new sections were added on “Signs and Symptoms of SCLC” and “Principles of Pathologic Review.”

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NCCN Guidelines Insights: Non–Small Cell Lung Cancer, Version 2.2021

Featured Updates to the NCCN Guidelines

David S. Ettinger, Douglas E. Wood, Dara L. Aisner, Wallace Akerley, Jessica R. Bauman, Ankit Bharat, Debora S. Bruno, Joe Y. Chang, Lucian R. Chirieac, Thomas A. D’Amico, Thomas J. Dilling, Jonathan Dowell, Scott Gettinger, Matthew A. Gubens, Aparna Hegde, Mark Hennon, Rudy P. Lackner, Michael Lanuti, Ticiana A. Leal, Jules Lin, Billy W. Loo Jr, Christine M. Lovly, Renato G. Martins, Erminia Massarelli, Daniel Morgensztern, Thomas Ng, Gregory A. Otterson, Sandip P. Patel, Gregory J. Riely, Steven E. Schild, Theresa A. Shapiro, Aditi P. Singh, James Stevenson, Alda Tam, Jane Yanagawa, Stephen C. Yang, Kristina M. Gregory, and Miranda Hughes

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non–Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.

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NCCN Guidelines Insights: Non–Small Cell Lung Cancer, Version 1.2020

Featured Updates to the NCCN Guidelines

David S. Ettinger, Douglas E. Wood, Charu Aggarwal, Dara L. Aisner, Wallace Akerley, Jessica R. Bauman, Ankit Bharat, Debora S. Bruno, Joe Y. Chang, Lucian R. Chirieac, Thomas A. D’Amico, Thomas J. Dilling, Michael Dobelbower, Scott Gettinger, Ramaswamy Govindan, Matthew A. Gubens, Mark Hennon, Leora Horn, Rudy P. Lackner, Michael Lanuti, Ticiana A. Leal, Jules Lin, Billy W. Loo Jr, Renato G. Martins, Gregory A. Otterson, Sandip P. Patel, Karen L. Reckamp, Gregory J. Riely, Steven E. Schild, Theresa A. Shapiro, James Stevenson, Scott J. Swanson, Kurt W. Tauer, Stephen C. Yang, Kristina Gregory, OCN, and Miranda Hughes

The NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates in immunotherapy. For the 2020 update, all of the systemic therapy regimens have been categorized using a new preference stratification system; certain regimens are now recommended as “preferred interventions,” whereas others are categorized as either “other recommended interventions” or “useful under certain circumstances.”

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NCCN Guidelines® Insights: Non–Small Cell Lung Cancer, Version 2.2023

Featured Updates to the NCCN Guidelines

David S. Ettinger, Douglas E. Wood, Dara L. Aisner, Wallace Akerley, Jessica R. Bauman, Ankit Bharat, Debora S. Bruno, Joe Y. Chang, Lucian R. Chirieac, Malcolm DeCamp, Thomas J. Dilling, Jonathan Dowell, Gregory A. Durm, Scott Gettinger, Travis E. Grotz, Matthew A. Gubens, Aparna Hegde, Rudy P. Lackner, Michael Lanuti, Jules Lin, Billy W. Loo Jr, Christine M. Lovly, Fabien Maldonado, Erminia Massarelli, Daniel Morgensztern, Thomas Ng, Gregory A. Otterson, Sandip P. Patel, Tejas Patil, Patricio M. Polanco, Gregory J. Riely, Jonathan Riess, Steven E. Schild, Theresa A. Shapiro, Aditi P. Singh, James Stevenson, Alda Tam, Tawee Tanvetyanon, Jane Yanagawa, Stephen C. Yang, Edwin Yau, Kristina M. Gregory, and Miranda Hughes

The NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) provide recommendations for management of disease in patients with NSCLC. These NCCN Guidelines Insights focus on neoadjuvant and adjuvant (also known as perioperative) systemic therapy options for eligible patients with resectable NSCLC.

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Non–Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology

David S. Ettinger, Douglas E. Wood, Dara L. Aisner, Wallace Akerley, Jessica R. Bauman, Ankit Bharat, Debora S. Bruno, Joe Y. Chang, Lucian R. Chirieac, Thomas A. D’Amico, Malcolm DeCamp, Thomas J. Dilling, Jonathan Dowell, Scott Gettinger, Travis E. Grotz, Matthew A. Gubens, Aparna Hegde, Rudy P. Lackner, Michael Lanuti, Jules Lin, Billy W. Loo Jr., Christine M. Lovly, Fabien Maldonado, Erminia Massarelli, Daniel Morgensztern, Thomas Ng, Gregory A. Otterson, Jose M. Pacheco, Sandip P. Patel, Gregory J. Riely, Jonathan Riess, Steven E. Schild, Theresa A. Shapiro, Aditi P. Singh, James Stevenson, Alda Tam, Tawee Tanvetyanon, Jane Yanagawa, Stephen C. Yang, Edwin Yau, Kristina Gregory, and Miranda Hughes

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non–Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.

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Mesothelioma: Peritoneal, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology

David S. Ettinger, Douglas E. Wood, James Stevenson, Dara L. Aisner, Wallace Akerley, Jessica R. Bauman, Ankit Bharat, Debora S. Bruno, Joe Y. Chang, Lucian R. Chirieac, Malcolm DeCamp, Thomas J. Dilling, Jonathan Dowell, Gregory A. Durm, Scott Gettinger, Travis E. Grotz, Matthew A. Gubens, Aparna Hegde, Rudy P. Lackner, Michael Lanuti, Jules Lin, Billy W. Loo Jr, Christine M. Lovly, Fabien Maldonado, Erminia Massarelli, Daniel Morgensztern, Trey C. Mullikin, Thomas Ng, Gregory A. Otterson, Sandip P. Patel, Tejas Patil, Patricio M. Polanco, Gregory J. Riely, Jonathan Riess, Theresa A. Shapiro, Aditi P. Singh, Alda Tam, Tawee Tanvetyanon, Jane Yanagawa, Stephen C. Yang, Edwin Yau, Kristina M. Gregory, and Miranda Hughes

Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM. The diagnosis of PeM may be delayed because PeM mimics other diseases and conditions and because the disease is so rare. The pathology section was recently updated to include new information about markers used to identify mesothelioma, which is difficult to diagnose. The term “malignant” is no longer used to classify mesotheliomas, because all mesotheliomas are now defined as malignant.