{"entity":{"id":"alex","kind":"trial","name":"ALEX","aka":[],"tldr":"ALEX showed that alectinib, a second-generation ALK drug that gets into the brain, kept ALK-positive lung cancer under control for about three years against less than one with crizotinib, and cut brain progression by three quarters.","summary":"ALEX randomised 303 patients with untreated advanced ALK-positive non-small-cell lung cancer to alectinib or crizotinib. Crizotinib had been the first ALK inhibitor, approved in 2011, but most patients progressed within a year, often in the brain, where the drug penetrates poorly.\n\nAt 12 months the cumulative incidence of brain progression was 9.4 percent with alectinib against 41.4 percent with crizotinib. In the updated analysis median investigator-assessed progression-free survival was 34.8 months against 10.9 months (hazard ratio 0.43), and five-year overall survival was 62.5 percent against 45.5 percent.\n\nThe FDA approved alectinib for first-line use in November 2017; the trial moved a second-generation inhibitor to the front and set the template that CROWN followed with lorlatinib.","status":"positive","asOf":"2026-09-17","links":[{"label":"ClinicalTrials.gov NCT02075840","url":"https://clinicaltrials.gov/study/NCT02075840"},{"label":"New England Journal of Medicine 2017","url":"https://doi.org/10.1056/NEJMoa1704795"},{"label":"Annals of Oncology 2020 (five-year survival)","url":"https://doi.org/10.1016/j.annonc.2020.04.478"}],"tags":[],"related":[],"cancers":["nsclc","alk-positive-nsclc"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["alk"],"drugs":["alectinib","crizotinib"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["brain-metastases","tki-term"],"trials":[],"people":["solange-peters","tony-mok","ross-camidge"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02075840","phase":"3","setting":"Untreated advanced ALK-positive non-small-cell lung cancer: alectinib versus crizotinib","sponsor":"Roche","result":"Median progression-free survival 34.8 vs 10.9 months (hazard ratio 0.43); 12-month brain progression 9.4% vs 41.4%; 5-year overall survival 62.5% vs 45.5%.","yearReported":2017,"enrolled":303,"outcomes":[{"endpoint":"Progression-free survival (investigator, updated)","primary":true,"unit":"months","arms":[{"name":"Alectinib","n":152,"value":34.8},{"name":"Crizotinib","n":151,"value":10.9}],"hr":0.43,"source":"https://doi.org/10.1016/j.annonc.2020.04.478"},{"endpoint":"Overall survival at 5 years","unit":"%","arms":[{"name":"Alectinib","n":152,"value":62.5},{"name":"Crizotinib","n":151,"value":45.5}],"source":"https://doi.org/10.1016/j.annonc.2020.04.478"}],"replication":"The Japanese J-ALEX trial reported the same direction; ALTA-1L (brigatinib) and CROWN (lorlatinib) confirmed that next-generation ALK inhibitors beat crizotinib first line."},"route":"/trials/alex/","neighbours":{"cancer":[{"id":"alk-positive-nsclc","kind":"cancer","name":"ALK-positive non-small-cell lung cancer","route":"/cancers/alk-positive-nsclc/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"alk","kind":"target","name":"ALK","route":"/targets/alk/"}],"drug":[{"id":"alectinib","kind":"drug","name":"Alectinib","route":"/drugs/alectinib/"},{"id":"crizotinib","kind":"drug","name":"Crizotinib","route":"/drugs/crizotinib/"}],"company":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"term":[{"id":"brain-metastases","kind":"term","name":"Brain metastases (intracranial disease)","route":"/terms/brain-metastases/"},{"id":"tki-term","kind":"term","name":"Tyrosine kinase inhibitor (TKI)","route":"/terms/tki-term/"}],"person":[{"id":"ross-camidge","kind":"person","name":"D. Ross Camidge","route":"/people/ross-camidge/"},{"id":"solange-peters","kind":"person","name":"Solange Peters","route":"/people/solange-peters/"},{"id":"tony-mok","kind":"person","name":"Tony S. K. Mok","route":"/people/tony-mok/"}]}}