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Some cancers reach the brain in up to a quarter of patients. Prevention trials could aim specifically at stopping that, instead of treating it once it has happened.
Brain-penetrant agents reduce central nervous system progression in metastatic disease, and adjuvant trials have shown CNS event reductions as secondary endpoints. No trial yet uses CNS-metastasis-free survival as a primary endpoint in a population prospectively defined as CNS-high-risk by subtype and risk score. This is a designable, ownable clinical setting rather than a new mechanism.
The survival benefit first reported in 2023 has held five years after the last dose of adjuvant osimertinib, which answers the worry that a three-year course only delays relapse. Patients with an exon 19 deletion gained most; the L858R estimate crosses one and is less certain. Nothing here changes the recommendation, which already rests on the 2023 analysis, but it tightens the case for testing every resected non-squamous tumour for EGFR mutations.
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.
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Anyone diagnosed with advanced lung cancer should have EGFR testing before treatment, because osimertinib as the first drug gives the longest disease control, protects the brain, and is well tolerated. Chemotherapy is not the first step for these patients. The remaining questions are whether to intensify upfront (adding chemotherapy or amivantamab) and how to treat resistance when it develops.
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 Measure brain metastasis prevention as a primary endpoint, not as a secondary one, Lorlatinib, Tucatinib, The brain: barrier and sanctuary.
Shares ALINA, HER2CLIMB, HER2-positive brain metastases, The brain: barrier and sanctuary.
Shares Measure brain metastasis prevention as a primary endpoint, not as a secondary one, FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer, Tucatinib, The brain: barrier and sanctuary.
Shares HER2CLIMB, HER2-positive brain metastases, Tucatinib, HER2-positive breast cancer.
Shares HER2CLIMB, HER2-positive brain metastases, Tucatinib, The brain: barrier and sanctuary.
Shares HER2-positive brain metastases, Alectinib, Lorlatinib, Tucatinib.
Shares Measure brain metastasis prevention as a primary endpoint, not as a secondary one, First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer, Alectinib, The brain: barrier and sanctuary.
Shares ALINA, Measure brain metastasis prevention as a primary endpoint, not as a secondary one, Alectinib, 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.