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The PD-L1 score used in lung cancer: the percentage of tumour cells that stain positive.
The tumour proportion score is the PD-L1 read-out used in non-small-cell lung cancer: the share of tumour cells that stain positive for PD-L1 on the 22C3 assay. A high score supports pembrolizumab or cemiplimab alone, an intermediate score favours chemo-immunotherapy, and a negative score still leaves room for chemo-immunotherapy or CTLA-4-containing regimens such as those tested in POSEIDON. Readers meet TPS in KEYNOTE-024 and KEYNOTE-189 and in the pairing of PD-1 blockade with chemotherapy in PD-L1-low disease. It differs from the combined positive score used in breast, gastric and head and neck cancer, which also counts immune cells. Its weakness as a predictor is why the biomarker-validation and immunotherapy-response bottlenecks link to it.
In plain words · PD-L1 is the tumour's side of the PD-1 brake, and also the biomarker that decides who gets immunotherapy.
Showing the target this term concerns: PD-L1.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
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.
Alongside the CheckMate trials this study replaced docetaxel with PD-1 blockade as second-line treatment for most lung cancers, and its PD-L1 threshold of 1% became the basis of pembrolizumab's label in previously treated disease.
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.
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 KEYNOTE-001 (Garon 2015): pembrolizumab in non-small-cell lung cancer and the 50% PD-L1 cut-off, CheckMate 057, CheckMate 017, IMpower110.
Shares CheckMate 057, CheckMate 017, KEYNOTE-010, PD-L1.
Shares CheckMate 057, CheckMate 017, KEYNOTE-010, CheckMate 9LA.
Shares KEYNOTE-010 (Herbst 2016): pembrolizumab versus docetaxel in previously treated PD-L1-positive lung cancer, KEYNOTE-024: pembrolizumab alone beats chemotherapy in PD-L1-high lung cancer, KEYNOTE-042, PD-L1.
Shares KEYNOTE-010 (Herbst 2016): pembrolizumab versus docetaxel in previously treated PD-L1-positive lung cancer, KEYNOTE-024: pembrolizumab alone beats chemotherapy in PD-L1-high lung cancer, KEYNOTE-042, PD-L1.
Shares PD-L1 TPS (tumour proportion score), No one can predict who responds to immunotherapy, Biomarkers are not validated or standardised, PD-L1.
Shares KEYNOTE-010 (Herbst 2016): pembrolizumab versus docetaxel in previously treated PD-L1-positive lung cancer, KEYNOTE-024: pembrolizumab alone beats chemotherapy in PD-L1-high lung cancer, PD-L1, Non-small-cell lung cancer.
Shares KEYNOTE-010 (Herbst 2016): pembrolizumab versus docetaxel in previously treated PD-L1-positive lung cancer, Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC, PD-L1-high non-small-cell lung cancer without a driver mutation, Pembrolizumab.