By Gregory J. Riely, MD
The changes seen in the 2018 update of the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for the treatment of patients with NSCLC reflect the rapid and significant progress we have observed in the treatment of lung cancer over the past 12 months. The currently posted NCCN Guidelines include all of the new approaches to treat patients with NSCLC that have so radically changed the NCCN recommendations.1
This latest update of the NCCN Guidelines contains new recommendations for identifying the “right patient for the right drug,” which has been the hallmark of lung cancer therapies for the past 10 years. To personalize therapy, the guidelines emphasize the need for knowledge of pretreatment tumor histology, molecular genotype, and immunophenotype prior to choosing therapy.
Recent additions include recommendations for osimertinib (category 2A) as an option for the first-line treatment of EGFR-mutant NSCLC, alectinib (category 1) as an option for the first-line treatment of ALK-positive NSCLC, ceritinib as an option (category 2A) for the first-line treatment of ROS-1 positive NSCLC, combination dabrafenib/trametinib (category 2A) for patients with BRAF V600Emutant NSCLC, and pembrolizumab (category 2A) as a single agent for the first-line treatment of patients with NSCLC who have PD-L1 expression of 50% or greater. Additionally, the 2018 NCCN Guidelines recommend the use of pembrolizumab in combination with carboplatin and pemetrexed as a treatment option for patients with metastatic NSCLC, based on the initial positive results from a phase II trial that were confirmed in a recent phase III trial.2 The clinical research data to support these recommendations were all presented or published in the last year.
In the 2018 update, a new section, “Principles of Molecular and Biomarker Analysis,” educates physicians about the continued development of molecular testing by describing the important molecular aberrations that must be identified and the best practices for testing. The NCCN Guidelines also continue to keep pace with new data for the “Emerging Targeted Agents for Patients with Genetic Alterations” section, describing recent studies that support testing and treatment for patients with MET exon 14 alterations, HER2 mutations, and RET gene rearrangements. Other recent additions are briefly outlined in the Summary of the Guidelines Updates (see the NCCN Guidelines for NSCLC, available at nccn.org).
The American Society of Clinical Oncology (ASCO) also issues guidelines for the treatment of NSCLC, although their guidelines have separate committees focusing on the treatment of early-stage disease or stage IV NSCLC, and guidelines are issued separately. The ASCO guidelines for systemic therapy of stage IV NSCLC are very rigorous in their assessment of evidence and, in the absence of strong evidence, are less likely to make a recommendation, compared to the NCCN Guidelines, which include a significant number of recommendations based on expert consensus. The ASCO guideline updates are issued less frequently (e.g., the most recently published guidelines, which became available on August 14, 2017, included a systematic review of evidence from February 2014 to December 2016). Because of the time needed for ASCO’s systematic review and the writing process, ASCO’s guidelines have not yet incorporated the first-line use of osimertinib for patients with EGFR-mutant NSCLC, the first-line use of alectinib for ALK-positive disease, or the data to support the combination of pembrolizumab with chemotherapy.
The NCCN Guidelines Process
NCCN is a not-for-profit alliance of 27 leading cancer centers whose mission is “improving the quality, effectiveness, and efficiency of cancer care.” NCCN is perhaps best known for the development of guidelines for treatment of patients with a variety of cancers, including small cell lung cancer and NSCLC. The goal of the NCCN Guidelines is to outline evidence-based, consensus-driven treatment to ensure that all patients get the best outcome. Key assets of the NCCN Guidelines include the staff who coordinate all aspects of review and development as well as the nature of the multidisciplinary panel, including thoracic surgeons, medical oncologists, radiation oncologists, pathologists, and molecular pathologists.
The NCCN Drugs & Biologics Compendium (NCCN Compendium®), which is derived from the Guidelines, is recognized by public and private insurers alike, including, but not limited to, the Centers for Medicare and Medicaid Services (CMS) and UnitedHealthcare, as an authoritative reference for oncology coverage policy. Annual reviews by NCCN member institutions serve as the foundation for changes in guidelines, and these are supplemented by a systematic review and submissions of recommendations from professional societies and others. Because the NCCN Guidelines are used by so many, the guidelines panel reacts quickly to incorporate new findings into its treatment recommendations. On this basis, the NCCN Guidelines for NSCLC were updated nine times in 2017 and already twice in 2018. The NCCN Guidelines, which are rapidly updated based on strong evidence and expert consensus, are presented in a clear, algorithmic fashion and are broadly accessible to guide oncologists in the best care available for patients today. ✦
NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.
About the Author: Dr. Riely is vice chair of the Clinical Trials Office, Department of Medicine at Memorial Sloan Kettering Cancer Institute. He is also an NCCN panel member for NSCLC.
1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Clinical Practice Guidelines in Oncology for the Treatment of Patients with NSCLC, 2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed. Accessed February 14, 2017. To view the most recent and complete version of the guideline, go online to NCCN.org.
2. Langer CJ, Gadgeel SM, Borghaei H, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, nonsquamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016;17:1497-1508.