# CheckMate 026: first-line nivolumab in stage IV or recurrent non-small-cell lung cancer

Source: https://onco.cc/key-papers/paper-checkmate-026-first-line-nivolumab-nejm-2017/  
OnCo record `paper-checkmate-026-first-line-nivolumab-nejm-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Giving an immunotherapy drug instead of chemotherapy as the first treatment did not help patients selected only by a moderate level of the PD-L1 protein. It is the trial that showed the threshold, not the drug, was the problem.

## Summary

Patients with untreated stage IV or recurrent non-small-cell lung cancer and a PD-L1 tumour-expression level of 1% or more were randomly assigned to nivolumab or platinum-based chemotherapy. Among the 423 patients with a PD-L1 expression level of 5% or more, median progression-free survival was 4.2 months with nivolumab against 5.9 months with chemotherapy (hazard ratio 1.15) and median overall survival was 14.4 against 13.2 months (hazard ratio 1.02); 60% of the chemotherapy group crossed over to nivolumab. Treatment-related adverse events of grade 3 or 4 occurred in 18% with nivolumab and 51% with chemotherapy.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: New England Journal of Medicine
- Year: 2017
- DOI: 10.1056/NEJMoa1613493
- Authors: Carbone DP, Reck M, Paz-Ares L, et al.
- Findings: No progression-free survival benefit at a PD-L1 threshold of 5% or more, hazard ratio 1.15.; Overall survival similar, hazard ratio 1.02, with 60% crossover.; Far fewer grade 3 or 4 adverse events with nivolumab.; An exploratory high mutation burden subgroup did better, which did not rescue the trial.
- What it means: Read beside the pembrolizumab trial that succeeded at a 50% threshold in the same setting, it is the cleanest demonstration that a PD-L1 threshold is not a property of the protein but of the trial that drew the line.
- Caveats: The comparison with the successful pembrolizumab trial is across trials, with different assays and populations.; Extensive crossover obscures the survival comparison.; The high burden subgroup analysis was exploratory and not powered.

## Sources

- Carbone et al., N Engl J Med 2017: CheckMate 026, first-line nivolumab in PD-L1-positive non-small-cell lung cancer: https://doi.org/10.1056/NEJMoa1613493
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28636851/

## Connected records

- biomarkers: [PD-L1 TC score (tumour-cell score, SP263 and 28-8)](https://onco.cc/biomarkers/pd-l1-tc-score/), [TMB-high (tumour mutational burden >= 10 mutations per megabase)](https://onco.cc/biomarkers/tmb-high/)
- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- technologies: [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [PD-1](https://onco.cc/targets/pd1/), [PD-L1](https://onco.cc/targets/pdl1/)
- drugs: [Nivolumab](https://onco.cc/drugs/nivolumab/)
- pathways: [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/)
- terms: [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/), [Tumour mutational burden (TMB)](https://onco.cc/terms/tmb/)
- people: [Martin Reck](https://onco.cc/people/martin-reck/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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