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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.
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.
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.
For the minority of patients whose tumours express a lot of PD-L1, a single antibody outperforms chemotherapy and is far easier to take. The word minority is the point: the same drug in the same disease at lower PD-L1 gives much less.
With CheckMate 017 in squamous disease, this trial ended docetaxel's reign as the default second-line treatment for lung cancer and established PD-1 blockade as standard after chemotherapy. Its PD-L1 finding shaped how later first-line trials were designed and how the biomarker is used in the clinic.
This trial gave lung cancer its immunotherapy biomarker. The 50% PD-L1 cut-off decides today whether a patient with advanced lung cancer can start immunotherapy alone or needs chemotherapy added, and the five-year follow-up later showed long-term survivors among first-line responders.
Shares CheckMate 057: nivolumab beats docetaxel after chemotherapy in non-squamous lung cancer, KEYNOTE-001 (Garon 2015): pembrolizumab in non-small-cell lung cancer and the 50% PD-L1 cut-off, Extended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stable, Randomised trials of stopping immunotherapy after one year versus continuing.
Shares KEYNOTE-024 & KEYNOTE-189, Tumour proportion score (TPS), PD-L1-high non-small-cell lung cancer without a driver mutation, PD-L1.
Shares Extended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stable, Randomised trials of stopping immunotherapy after one year versus continuing, Tumour proportion score (TPS), PD-L1-high non-small-cell lung cancer without a driver mutation.
Shares Martin Reck, Immunohistochemistry (IHC), PD-1 / PD-L1 immune checkpoint & T-cell activation, Histopathology & immunohistochemistry.
Shares KEYNOTE-024 & KEYNOTE-189, Tumour proportion score (TPS), PD-L1-high non-small-cell lung cancer without a driver mutation, PD-L1.
Shares KEYNOTE-024 & KEYNOTE-189, Tumour proportion score (TPS), PD-L1-high non-small-cell lung cancer without a driver mutation, Pembrolizumab.
Shares PD-L1 TPS (tumour proportion score), Immunohistochemistry (IHC), PD-1 / PD-L1 immune checkpoint & T-cell activation, Histopathology & immunohistochemistry.
Shares KEYNOTE-024 & KEYNOTE-189, Tumour proportion score (TPS), PD-L1-high non-small-cell lung cancer without a driver mutation, PD-L1.