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In the patients whose tumours showed the most PD-L1, immunotherapy alone gave a median survival of 20.2 months against 13.1 on chemotherapy, with far fewer severe side effects.
Herbst, Giaccone, de Marinis and colleagues randomised 572 patients with metastatic non-squamous or squamous non-small-cell lung cancer, untreated and with PD-L1 expression on at least 1 percent of tumour cells or tumour-infiltrating immune cells by the SP142 assay, 1 to 1 between atezolizumab and platinum-based chemotherapy. Overall survival was tested hierarchically by PD-L1 status among patients whose tumours were EGFR and ALK wild-type.
IMpower110 is the trial that generalised KEYNOTE-024's result to a second drug and a second assay, and in doing so exposed the assay problem: SP142, 22C3 and SP263 score different things and select different patients, so PD-L1 high means different populations in different trials.
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.
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 study is why PD-1 inhibitors were developed across cancers rather than in melanoma alone: unexpected activity in lung cancer, historically thought immune-resistant, changed drug development priorities industry-wide. It also introduced PD-L1 immunohistochemistry as a candidate biomarker and pneumonitis as a signature toxicity. Within five years PD-1 blockade was approved in more than ten cancers.
Shares Immune checkpoint, PD-L1-high non-small-cell lung cancer without a driver mutation, 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, Immunohistochemistry (IHC) and the tag lung-evidence.
Shares Immune checkpoint, 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, No one can predict who responds to immunotherapy, PD-1 and the tag lung-evidence.
Shares Immune checkpoint, 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, No one can predict who responds to immunotherapy, PD-L1 and the tag lung-evidence.
Shares Immune checkpoint, 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, No one can predict who responds to immunotherapy, Biomarkers are not validated or standardised and the tag lung-evidence.
Shares Immune checkpoint, 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, No one can predict who responds to immunotherapy, Biomarkers are not validated or standardised and the tag lung-evidence.
Shares 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, Biomarkers are not validated or standardised, Roche / Genentech, New England Journal of Medicine and the tag lung-evidence.
Shares 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, Biomarkers are not validated or standardised, New England Journal of Medicine, Cisplatin and the tag lung-evidence.
Shares Immune checkpoint, 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, No one can predict who responds to immunotherapy, PD-L1 and the tag lung-evidence.