NCCN Guidelines® Insights: Non-Small Cell Lung Cancer, Version 7.2025
- Study type
- Clinical guideline
- Study name
- NCCN NSCLC v7.2025 (Insights)
- Design
- Clinical guideline based on evidence and consensus of the NCCN multidisciplinary panel
- Source
- J Natl Compr Canc Netw · 2025
In plain words
This US guideline explains that in lung cancer that can be operated on, with a tumour larger than 4 cm or with spread to lymph nodes, a combination of chemotherapy and immunotherapy is usually recommended before surgery, and that before this the tumour should be tested for EGFR and ALK mutations, because patients with these mutations benefit more from targeted tablets (osimertinib or alectinib) after surgery.
Key guideline recommendations
Patients with tumours ≥4 cm or lymph node involvement should be evaluated for preoperative therapy, and use of an immune checkpoint inhibitor with chemotherapy should be strongly considered.
- NCCN category 1
Three perioperative regimens are recommended: (1) nivolumab with platinum doublet chemotherapy before surgery, then single-agent nivolumab after surgery (in the absence of a known EGFR mutation or ALK rearrangement); (2) pembrolizumab with cisplatin-based doublet chemotherapy before surgery, then single-agent pembrolizumab after surgery; (3) durvalumab with platinum doublet chemotherapy before surgery, then single-agent durvalumab after surgery (in the absence of an EGFR mutation or ALK rearrangement).
In general, perioperative therapy should be given with a single regimen, and switching the type of immunotherapy is not recommended.
- NCCN category 1
Alectinib has been added as an adjuvant treatment option for patients with completely resected ALK-rearranged NSCLC (tumour ≥4 cm or lymph node involvement).
- NCCN category 1
Osimertinib remains recommended for selected patients with completely resected NSCLC with exon 19 deletion or L858R mutation who have received prior adjuvant chemotherapy or are not eligible for platinum-based chemotherapy.
- NCCN category 1 in stage III; category 2A in stage II
In unresectable stage II or III NSCLC with performance status 0–1 and no progression after definitive concurrent chemoradiotherapy, two consolidation options are recommended: osimertinib for tumours with exon 19 deletion or L858R, and durvalumab for tumours without these mutations.
Testing for EGFR mutation and ALK rearrangement is recommended in patients with stage IB to IIIA or IIIB (T3–4, N2) disease to inform decisions on neoadjuvant and/or adjuvant systemic therapy; EGFR testing is also recommended in stage IIIC. In stages I to III, tissue testing is preferred, and ctDNA testing is not routinely recommended because of its lower sensitivity.
Possible contraindications to PD-1/PD-L1 inhibitors such as durvalumab include active or previous autoimmune disease and/or current use of immunosuppressive drugs; some oncogenic drivers (EGFR, ALK, RET, ROS1) have been associated with less benefit from these drugs.
Study population
Patients with non-metastatic NSCLC (resectable and unresectable stage II–III) and the related molecular testing.
Clinical significance and place in guidelines
This guideline establishes the place of CheckMate 816, KEYNOTE-671, AEGEAN, ADAURA, ALINA, PACIFIC and LAURA in clinical practice and underpins the “treatment by stage” section of the lung cancer page. The full, current guideline is freely available at NCCN.org.
Limitations
This paper is a selected summary of the full guideline; NCCN guidelines are updated regularly and are based on the US health system and FDA approvals. No trial has directly compared the three strategies of neoadjuvant, perioperative and adjuvant therapy.
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.