# KEYNOTE-024: pembrolizumab alone beats chemotherapy in PD-L1-high lung cancer

Source: https://onco.cc/key-papers/paper-keynote-024-nejm-2016/  
OnCo record `paper-keynote-024-nejm-2016` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In patients whose lung tumours carried PD-L1 on at least half their cells, pembrolizumab alone held the cancer back longer than chemotherapy and caused fewer serious side effects, making immunotherapy the first treatment for this group.

## Summary

KEYNOTE-024 randomised 305 patients with untreated advanced non-small-cell lung cancer, a PD-L1 tumour proportion score of 50% or more and no EGFR or ALK alteration to pembrolizumab or platinum-based chemotherapy. Pembrolizumab improved progression-free survival, the primary endpoint, and overall survival at the interim analysis, with a higher response rate and fewer grade 3 to 5 adverse events, and patients on chemotherapy could cross over at progression. Five-year follow-up later confirmed the survival advantage. The trial made PD-L1 testing routine at lung cancer diagnosis and established chemotherapy-free first-line immunotherapy for the PD-L1-high group.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2016
- DOI: 10.1056/NEJMoa1606774
- Authors: Reck M, Rodríguez-Abreu D, Robinson AG, et al.
- Findings: 305 patients with PD-L1 tumour proportion score of 50% or more; pembrolizumab vs platinum doublet chemotherapy.; Median progression-free survival 10.3 vs 6.0 months, hazard ratio 0.50.; Overall survival hazard ratio 0.60 at the interim analysis; estimated six-month survival 80.2% vs 72.4%.; Response rate 44.8% vs 27.8%; grade 3 to 5 treatment-related adverse events 26.6% vs 53.3%.
- What it means: This trial is why PD-L1 is measured on every new advanced lung cancer and why a patient with a high score can start immunotherapy without chemotherapy. Together with KEYNOTE-189 for the rest of the population, it moved checkpoint inhibitors from second-line rescue to the first treatment most lung cancer patients receive.
- Caveats: Applies only to the roughly 30% of patients with a PD-L1 score of 50% or more and no EGFR or ALK driver.; Crossover from chemotherapy to pembrolizumab affected the survival comparison.; PD-L1 testing varies by assay and is imperfect as a predictor within the eligible group.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa1606774
- ClinicalTrials.gov NCT02142738: https://clinicaltrials.gov/study/NCT02142738

## Connected records

- roadmaps: [Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch](https://onco.cc/roadmaps/lung-cancer-evidence-roadmap/)
- key papers: [Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC](https://onco.cc/key-papers/paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020/), [CheckMate 057: nivolumab beats docetaxel after chemotherapy in non-squamous lung cancer](https://onco.cc/key-papers/paper-checkmate-057-nejm-2015/), [KEYNOTE-001 (Garon 2015): pembrolizumab in non-small-cell lung cancer and the 50% PD-L1 cut-off](https://onco.cc/key-papers/paper-keynote-001-pembrolizumab-nsclc-nejm-2015/)
- biomarkers: [PD-L1 TPS (tumour proportion score)](https://onco.cc/biomarkers/pd-l1-tps/)
- cancers: [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [PD-L1-high non-small-cell lung cancer without a driver mutation](https://onco.cc/cancers/pdl1-high-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: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- companies: [Merck & Co. (MSD)](https://onco.cc/companies/merck/)
- pathways: [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/)
- terms: [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/), [Overall survival (OS)](https://onco.cc/terms/os/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/), [Tumour proportion score (TPS)](https://onco.cc/terms/tps/)
- trials: [KEYNOTE-024 & KEYNOTE-189](https://onco.cc/trials/keynote-024-189/)
- people: [Martin Reck](https://onco.cc/people/martin-reck/)
- ideas: [Extended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stable](https://onco.cc/ideas/idea-tr1-extended-interval-checkpoint-dosing/), [Randomised trials of stopping immunotherapy after one year versus continuing](https://onco.cc/ideas/idea-tr1-immunotherapy-stop-trials/)

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