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The large early trial that showed pembrolizumab shrinks about a fifth of advanced lung cancers, with responses that last, and that identified a PD-L1 score of 50% or more as the group most likely to benefit.
KEYNOTE-001 treated 495 patients with advanced non-small-cell lung cancer, both previously treated and untreated, with pembrolizumab at several doses and schedules. The overall response rate was about 19% with a median duration of response around a year and no clear difference between doses. A training and validation approach on PD-L1 immunohistochemistry defined a tumour proportion score of at least 50% as the threshold at which response and survival were markedly better, a cut-off adopted by KEYNOTE-024 and now used in clinics worldwide.
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.
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.
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, Objective response rate (ORR), 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.
Shares Tumour proportion score (TPS), PD-L1 expression testing (22C3, SP142, SP263), PD-L1-high non-small-cell lung cancer without a driver mutation, PD-L1.
Shares Tumour proportion score (TPS), PD-L1 expression testing (22C3, SP142, SP263), PD-L1-high non-small-cell lung cancer without a driver mutation, PD-L1.
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, PD-1.
Shares PD-L1-high non-small-cell lung cancer without a driver mutation, Merck & Co. (MSD), Pembrolizumab, Non-small-cell lung cancer.
Shares Tumour proportion score (TPS), PD-L1 expression testing (22C3, SP142, SP263), PD-L1, PD-1.
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, PD-1.
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, PD-1.