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CROWN's third-generation ALK drug kept 78 percent of patients free of progression at a year against 39 percent on crizotinib, and controlled disease inside the brain far better.
The CROWN trial investigators, reported by Shaw, Bauer, de Marinis and colleagues with Solomon as senior author, randomised 296 patients with advanced ALK-positive non-small-cell lung cancer and no previous systemic treatment for metastatic disease between lorlatinib and crizotinib. The primary endpoint was blinded independent central review progression-free survival; intracranial response was a secondary endpoint.
The cost is a distinctive toxicity profile: hyperlipidaemia and central nervous system effects on mood, speed and memory. Lorlatinib is the first lung cancer drug whose main side effect is cognitive, which makes the choice between it and alectinib a quality-of-life question rather than a purely efficacy one.
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.
Shares Measure brain metastasis prevention as a primary endpoint, not as a secondary one, Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer, Brain metastases (intracranial disease), ALK-positive non-small-cell lung cancer and the tag lung-evidence.
Shares Measure brain metastasis prevention as a primary endpoint, not as a secondary one, Prevention trials aimed only at brain metastasis, Brain metastases (intracranial disease), The brain: barrier and sanctuary and the tag lung-evidence.
Shares Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer, Crizotinib, 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 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, Drug resistance (primary and acquired), Acquired resistance to every therapy, Toxicity and quality of life are undervalued and the tag lung-evidence.
Shares 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, Drug resistance (primary and acquired), Acquired resistance to every therapy 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, Toxicity and quality of life are undervalued, 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, Drug resistance (primary and acquired), Acquired resistance to every therapy, 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, Acquired resistance to every therapy, Toxicity and quality of life are undervalued, New England Journal of Medicine and the tag lung-evidence.