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1,500 tumours were screened to find 82 patients with an ALK fusion. Of those, 57 percent responded to crizotinib, a drug originally developed against a different target.
Kwak, Bang, Camidge, Shaw and colleagues screened tumour samples from approximately 1,500 patients with non-small-cell lung cancer for ALK rearrangements and enrolled 82 with advanced ALK-positive disease into an expanded cohort of the phase 1 study of crizotinib at 250 mg twice daily.
The screening ratio is the story as much as the response rate. Finding 82 eligible patients took 1,500 assays, which is the infrastructure cost of precision oncology stated plainly, and the reason molecular testing had to become routine rather than trial-specific.
The trial that made ALK testing worth doing. It is also the clearest case in oncology of a drug finding its disease after the fact: crizotinib entered the clinic as a MET inhibitor and became an ALK drug because somebody checked.
The current first choice for ALK-positive lung cancer in most guidelines, and the strongest evidence in solid tumour oncology that a drug can be designed to work inside the brain. Five-year follow-up has since shown the majority of patients still progression-free.
First-line ALK treatment moved to a drug designed for the brain, and brain metastasis prevention became an explicit design goal rather than a hoped-for side effect. ALK-positive lung cancer is now among the longest-surviving metastatic solid tumours.
One of the most cited trial reports Europe PMC returns for ALK in Non-small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
The second driver in lung cancer, and the one that proved the first was not a special case. It also established mutual exclusivity as a working assumption: a tumour usually has one driver, so finding it tells you what to give.
Shares Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer, Brain metastases (intracranial disease), ALK-positive non-small-cell lung cancer, 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 and the tag lung-evidence.
Shares Driver mutation, Next-generation sequencing (NGS), MET, 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 and the tag lung-evidence.
Shares Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer, First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer, Brain metastases (intracranial disease), The brain: barrier and sanctuary and the tag lung-evidence.
Shares Oncogene addiction, Massachusetts General Hospital Cancer Center, Driver mutation, Next-generation sequencing (NGS) and the tag lung-evidence.
Shares Oncogene addiction, Driver mutation, Next-generation sequencing (NGS), 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 and the tag lung-evidence.
Shares Driver mutation, Next-generation sequencing (NGS), MET, 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 and the tag lung-evidence.
Shares Oncogene addiction, Driver mutation, Next-generation sequencing (NGS), 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 and the tag lung-evidence.
Shares Brain metastases (intracranial disease), 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, Trials enrol too few, too slowly, Biomarkers are not validated or standardised and the tag lung-evidence.