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Lung cancer spreads to the brain more than any other common cancer, and the newest drugs seem to stop it happening. Almost no trial is designed to prove that, so the claim stays a footnote.
Prophylactic cranial irradiation is the proof of principle: Aupérin's overview of 987 patients showed that treating a brain with no visible disease in it extends life in small-cell lung cancer. In non-small-cell disease, alectinib, lorlatinib and osimertinib all appear to prevent as well as treat central nervous system disease, and CROWN's intracranial response figures and ALINA's central nervous system disease-free survival are the strongest evidence for it. But these are secondary endpoints, measured with inconsistent imaging schedules, in trials powered for something else.
The idea is to design for it: brain-metastasis-free survival as a primary endpoint, with protocol-mandated MRI at fixed intervals, in the populations where the risk is highest. Prevention of brain metastases is a distinct clinical good, and the current evidence base does not let anyone say by how much any drug delivers it.
Adjuvant treatment for lung cancer is now chosen by genotype. A resected ALK-positive tumour is treated with two years of a tablet instead of four cycles of platinum, which is a different life as well as a different outcome.
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.
Treating the brain before the cancer gets there works in small-cell lung cancer, and it is the proof of principle behind every later attempt to prevent rather than treat brain metastases.
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 Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission, Radiotherapy, 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 and the tag lung-evidence.
Shares Alectinib in resected ALK-positive non-small-cell lung cancer, Radiotherapy, 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, Trial design, endpoints and cost and the tag lung-evidence.
Shares Radiotherapy, 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, Trial design, endpoints and cost, Lung cancer (all types) and the tag lung-evidence.
Shares Prophylactic cranial irradiation vs MRI surveillance, Radiotherapy, 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, Lung cancer (all types) 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, EGFR-mutated non-small-cell lung cancer, Lung cancer (all types) 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, Lung cancer (all types) and the tag lung-evidence.
Shares Radiotherapy, 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, EGFR-mutated non-small-cell lung cancer, Lung cancer (all types) and the tag lung-evidence.