Non–small cell lung cancer (NSCLC) can no longer be considered as one disease, nor can it be treated as one. Understanding tumor histology in NSCLC is critical to understanding optimal biomarker evaluation and initial therapy. Proper biomarker evaluation includes both evaluation of PD-L1 status, as well as testing for actionable oncogenic drivers such as EGFR, ALK, ROS1, BRAF, Met Exon 14, RET, and NTRK. For patients with NSCLC and a driver oncogene, preferred treatment is targeted therapy. Conversely, for those without an oncogenic driver, preferred initial treatment is pembrolizumab in combination with chemotherapy for patients with low PD-L1 expression (1%–49%) or as a single-agent for high PD-L1 expression (≥50%). For small cell lung cancer (SCLC), the first major NCCN Guideline changes occurred in 2019, with the addition of either atezolizumab or durvalumab to platinum-based chemotherapy and etoposide as first-line therapy for patients with extensive-stage SCLC.
Presenter: Gregory J. Riely
Helena A. Yu and Gregory J. Riely
EGFR mutations identify patients who are more likely to respond to treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) than cytotoxic chemotherapy. The distinct success of the first-generation EGFR TKIs erlotinib and gefitinib has been accompanied by the observation that acquired resistance to these treatments develops after a median of 1 year of treatment. Newer, second-generation EGFR TKIs have been developed with the intent to delay or overcome acquired resistance by the broader inhibition of kinases (eg, HER2 and vascular endothelial growth factor receptor) and/or altering the interactions with EGFR through irreversibly binding to the kinase domain. This article discusses many of these agents (including afatinib, dacomitinib, XL647, AP26113, and CO-1686) which have the potential for greater efficacy compared with first-generation EGFR TKIs, and may also have clinical activity against other oncogenic mutations within the EGFR family, including HER2.
Presenters: Jane Yanagawa and Gregory J. Riely
For patients with resectable non–small cell lung cancer (NSCLC) as well as those with metastatic disease, there have been significant recent advances in therapies. In patients with resectable disease, new evidence supports use of neoadjuvant nivolumab + chemotherapy for eligible patients with resectable stage II–IIIA NSCLC. Separate data lead to the recommendation for adjuvant atezolizumab (after adjuvant chemotherapy) for eligible patients with completely resected stage II–IIIA NSCLC and PD-L1 expression ≥1%. Adjuvant osimertinib (± adjuvant chemotherapy) is an alternative for eligible patients with completely resected stage IB–IIIA NSCLC and EGFR mutations (exon 19 del or L858R). For patients with metastatic NSCLC, molecular testing is recommended for EGFR and BRAF mutations; MET exon skipping 14 alterations; ALK, ROS1, RET, and NTRK1/2/3 gene arrangements; and KRAS G12C mutations. First-line targeted therapies are available for many of these targets and, in the second-line setting, there are new targeted agents for KRAS G12C mutations and EGFR exon 20 insertions.
Presenters: Dara L. Aisner and Gregory J. Riely
Updates to the NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) for 2021 include recommendations for biomarker testing in all appropriate patients with newly diagnosed advanced lung cancer, including squamous cell lung cancer. When a targetable genetic alteration is detected, the NCCN Guidelines recommend treatment with a first-line therapy targeted to that alteration. The guidelines contain new information on use of adjuvant treatment with osimertinib for resected early-stage EGFR-mutated NSCLC. New targeted agents are now recommended for the treatment of ALK rearrangements, RET alterations, MET exon 14 skipping mutations in patients with advanced NSCLC; and new immunotherapy agents are recommended for advanced NSCLC without a driver oncogene.
Gregory J. Riely, Jamie E. Chaft, Marc Ladanyi, and Mark G. Kris
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.
David S. Ettinger, Douglas E. Wood, Wallace Akerley, Lyudmila A. Bazhenova, Hossein Borghaei, David Ross Camidge, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D’Amico, Todd L. Demmy, Thomas J. Dilling, Ramaswamy Govindan, Frederic W. Grannis Jr, Leora Horn, Thierry M. Jahan, Ritsuko Komaki, Mark G. Kris, Lee M. Krug, Rudy P. Lackner, Michael Lanuti, Rogerio Lilenbaum, Jules Lin, Billy W. Loo Jr, Renato Martins, Gregory A. Otterson, Jyoti D. Patel, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Eric Rohren, Steven Schild, Theresa A. Shapiro, Scott J. Swanson, Kurt Tauer, Stephen C. Yang, Kristina Gregory, and Miranda Hughes
This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) focuses on the principles of radiation therapy (RT), which include the following: (1) general principles for early-stage, locally advanced, and advanced/metastatic NSCLC; (2) target volumes, prescription doses, and normal tissue dose constraints for early-stage, locally advanced, and advanced/palliative RT; and (3) RT simulation, planning, and delivery. Treatment recommendations should be made by a multidisciplinary team, including board-certified radiation oncologists who perform lung cancer RT as a prominent part of their practice.
David S. Ettinger, Gregory J. Riely, Wallace Akerley, Hossein Borghaei, Andrew C. Chang, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D’Amico, Todd L. Demmy, Ramaswamy Govindan, Frederic W. Grannis Jr, Stefan C. Grant, Leora Horn, Thierry M. Jahan, Ritsuko Komaki, Feng-Ming (Spring) Kong, Mark G. Kris, Lee M. Krug, Rudy P. Lackner, Inga T. Lennes, Billy W. Loo Jr, Renato Martins, Gregory A. Otterson, Jyoti D. Patel, Mary C. Pinder-Schenck, Katherine M. Pisters, Karen Reckamp, Eric Rohren, Theresa A. Shapiro, Scott J. Swanson, Kurt Tauer, Douglas E. Wood, Stephen C. Yang, Kristina Gregory, and Miranda Hughes
Masses in the anterior mediastinum can be neoplasms (eg, thymomas, thymic carcinomas, or lung metastases) or non-neoplastic conditions (eg, intrathoracic goiter). Thymomas are the most common primary tumor in the anterior mediastinum, although they are rare. Thymic carcinomas are very rare. Thymomas and thymic carcinomas originate in the thymus. Although thymomas can spread locally, they are much less invasive than thymic carcinomas. Patients with thymomas have 5-year survival rates of approximately 78%. However, 5-year survival rates for thymic carcinomas are only approximately 40%. These guidelines outline the evaluation, treatment, and management of these mediastinal tumors.
David S. Ettinger, Wallace Akerley, Hossein Borghaei, Andrew C. Chang, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D’Amico, Todd L. Demmy, Apar Kishor P. Ganti, Ramaswamy Govindan, Frederic W. Grannis Jr, Leora Horn, Thierry M. Jahan, Mohammad Jahanzeb, Anne Kessinger, Ritsuko Komaki, Feng-Ming (Spring) Kong, Mark G. Kris, Lee M. Krug, Inga T. Lennes, Billy W. Loo Jr, Renato Martins, Janis O’Malley, Raymond U. Osarogiagbon, Gregory A. Otterson, Jyoti D. Patel, Mary C. Pinder-Schenck, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Eric Rohren, Scott J. Swanson, Douglas E. Wood, Stephen C. Yang, Miranda Hughes, and Kristina M. Gregory
Most patients with non–small cell lung cancer (NSCLC) are diagnosed with advanced cancer. These guidelines only include information about stage IV NSCLC. Patients with widespread metastatic disease (stage IV) are candidates for systemic therapy, clinical trials, and/or palliative treatment. The goal is to identify patients with metastatic disease before initiating aggressive treatment, thus sparing these patients from unnecessary futile treatment. If metastatic disease is discovered during surgery, then extensive surgery is often aborted. Decisions about treatment should be based on multidisciplinary discussion.