Non–Small Cell Lung Cancer Clinical Practice Guidelines (NCCN, 2022)

National Comprehensive Cancer Network

These are some of the highlights of the guidelines without analysis or commentary. For more information, go directly to the guidelines by clicking the link in the reference.

May 31, 2022

Updated guidelines on the management of non–small cell lung cancer (NSCLC) were published in May 2022 by the National Comprehensive Cancer Network (NCCN), in the Journal of the National Comprehensive Cancer Network.[1]

Molecular testing for actionable oncogenic driver mutations and programmed death ligand 1 (PD-L1) is recommended in all patients with metastatic nonsquamous NSCLC and NSCLC not otherwise specified (NOS), and should be considered in all patients with metastatic squamous cell NSCLC. Testing should be performed before initiating treatment, if feasible.

Single-agent targeted therapy is recommended for patients with actionable driver mutations (ie, ALK fusion, EGFR activating mutations, METex14 skipping, NTRK1/2/3 fusions, RET rearrangements, ROS1 rearrangements) or those with emerging driver mutations.

Recommended agents for patients with ALK-positive metastatic NSCLC are alectinib, brigatinib, ceritinib, crizotinib, and lorlatinib.

Dabrafenib plus trametinib is a preferred first-line therapy option for patients with metastatic NSCLC and BRAF p.V600E mutations.

Chemotherapy/immunotherapy regimens are recommended for patients without targetable somatic variants/mutations.

Chemotherapy/immunotherapy regimens, such as pembrolizumab/carboplatin (or cisplatin)/pemetrexed, are recommended for patients with metastatic nonsquamous NSCLC and negative test results for actionable driver mutations (ie, wild type), regardless of PD-L1 expression.

Patients with metastatic NSCLC and PD-L1 expression levels of 1% or more—but who also have a targetable driver oncogene molecular variant—should receive first-line targeted therapy for that oncogene and not first-line immune checkpoint inhibitor therapy.

In patients with metastatic NSCLC, recommended targeted therapy based on emerging biomarkers (using agents not approved by the US Food and Drug Administration for lung cancer) include capmatinib, crizotinib, or tepotinib for high-level MET amplification; and ado-trastuzumab emtansine or fam-trastuzumab deruxtecan-nxki for ERBB2 (HER2) mutations.

For more information, please go to Non–Small Cell Lung Cancer (NSCLC).


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