Non-Small Cell Lung Cancer, Version 4.2026, NCCN Clinical Practice Guidelines In Oncology
- Study type
- Clinical guideline
- Study name
- NCCN NSCLC v4.2026
- Design
- Clinical guideline based on evidence and consensus of the NCCN multidisciplinary panel
- Source
- J Natl Compr Canc Netw · 2026
In plain words
This US guideline stresses that in advanced lung cancer, the tumour should be tested for genetic changes before treatment starts, because for many of these changes (such as EGFR, ALK, ROS1, BRAF, MET and RET) there are targeted tablets or drugs that are often more effective and easier to tolerate than chemotherapy.
Key guideline recommendations
To identify the most appropriate initial therapy, the histological subtype should be determined and biomarker testing performed before starting systemic therapy.
- NCCN category 1, preferred
In the first line for advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation, preferred options are: single-agent osimertinib, osimertinib with (carboplatin or cisplatin)/pemetrexed (in non-squamous histology), or lazertinib with amivantamab.
- Preferred
For EGFR S768I, L861Q and/or G719X mutations, afatinib or osimertinib are preferred first-line options.
- NCCN category 1, preferred
In non-squamous NSCLC with an EGFR exon 20 insertion mutation, amivantamab with carboplatin and pemetrexed is the preferred first-line option.
- NCCN category 1
In NSCLC with an ALK gene fusion, alectinib, brigatinib, ensartinib or lorlatinib are preferred first-line options; ceritinib and crizotinib are useful in certain circumstances. If the ALK fusion is discovered before first-line therapy, all of these options are category 1 recommendations.
- Preferred
In NSCLC with a ROS1 fusion, crizotinib, entrectinib, repotrectinib or taletrectinib are preferred first-line options; entrectinib, repotrectinib or taletrectinib may be better for patients with brain metastases.
- Preferred
For BRAF V600E mutation, dabrafenib/trametinib or encorafenib/binimetinib are preferred first-line options.
- Preferred
For MET exon 14 skipping mutation, capmatinib or tepotinib are preferred and crizotinib is “useful in certain circumstances”; for RET fusion, pralsetinib or selpercatinib are preferred (selpercatinib category 1). Switching between drugs with a similar mechanism at progression is not recommended.
In NSCLC with a KRAS G12C mutation, the choice of first-line systemic therapy (immunotherapy and/or chemotherapy) is based on the level of PD-L1 expression.
In NSCLC with an ERBB2 (HER2) mutation or NRG1 fusion, first-line treatment uses standard systemic regimens (chemotherapy with or without immunotherapy); data suggest that single-agent immunotherapy may be less effective with HER2 mutations.
Study population
Patients with advanced or metastatic NSCLC with actionable biomarkers (EGFR, ALK, ROS1, BRAF, NTRK, MET, RET, KRAS G12C, HER2, NRG1).
Clinical significance and place in guidelines
This version of the NCCN guideline turns the results of FLAURA2, MARIPOSA and CROWN into preferred first-line recommendations and underpins the “biomarkers and targeted therapy” table on the lung cancer page.
Limitations
The excerpt published in JNCCN covers only the treatment of advanced disease with an actionable biomarker; the full version is at NCCN.org. Some drugs are not approved or not available in Europe or other regions.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.