{"entity":{"id":"paper-kwak-crizotinib-alk-nsclc-nejm-2010","kind":"paper","name":"Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer","aka":[],"tldr":"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.","summary":"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.\n\nThe 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.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2010","url":"https://doi.org/10.1056/NEJMoa1006448"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20979469/"},{"label":"ClinicalTrials.gov NCT00585195","url":"https://clinicaltrials.gov/study/NCT00585195"}],"tags":["lung-evidence"],"related":["paper-soda-eml4-alk-fusion-nature-2007","paper-alk-nsclc-n-engl-j-med-2013","paper-peters-alex-alectinib-crizotinib-nejm-2017","paper-shaw-crizotinib-ros1-nejm-2014"],"cancers":["lung-cancer","nsclc","alk-positive-nsclc"],"sections":["targeted-therapy"],"technologies":["fish","ngs","kinase-inhibitors"],"targets":["alk","met"],"drugs":["crizotinib"],"companies":["pfizer"],"institutions":["mgh"],"pathways":[],"terms":["driver-mutation","oncogene-addiction","brain-metastases"],"trials":[],"people":["alice-shaw"],"bottlenecks":["b-biomarker-validation","b-brain-delivery","b-trial-enrolment"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2010,"doi":"10.1056/NEJMoa1006448","pmid":"20979469","authors":"Kwak EL, Bang YJ, Camidge DR, et al.","paperType":"rct","findings":["Overall response rate 57 percent (47 of 82 patients: 46 confirmed partial responses and 1 confirmed complete response) at a mean treatment duration of 6.4 months.","27 patients (33 percent) had stable disease.","63 of 82 patients (77 percent) were still receiving crizotinib at data cutoff; estimated six-month progression-free survival 72 percent, with no median reached.","Side effects were mild grade 1 or 2 gastrointestinal events.","Approximately 1,500 patients were screened to identify the 82 with ALK rearrangements; those patients tended to be younger, with little or no tobacco exposure, and had adenocarcinomas."],"whatItMeans":"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.","caveats":["Single-arm expanded phase 1 cohort, not randomised; the randomised comparison against chemotherapy came in PROFILE 1007 (paper-alk-nsclc-n-engl-j-med-2013).","Median progression-free survival was not reached at 6.4 months of follow-up, so durability could not be judged.","Crizotinib penetrates the central nervous system poorly, and brain progression became the dominant failure pattern; the next-generation inhibitors were built for that."],"changedPractice":true,"participants":82},"route":"/key-papers/paper-kwak-crizotinib-alk-nsclc-nejm-2010/","neighbours":{"paper":[{"id":"paper-peters-alex-alectinib-crizotinib-nejm-2017","kind":"paper","name":"Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer","route":"/key-papers/paper-peters-alex-alectinib-crizotinib-nejm-2017/"},{"id":"paper-shaw-crizotinib-ros1-nejm-2014","kind":"paper","name":"Crizotinib in ROS1-rearranged non-small-cell lung cancer","route":"/key-papers/paper-shaw-crizotinib-ros1-nejm-2014/"},{"id":"paper-alk-nsclc-n-engl-j-med-2013","kind":"paper","name":"Crizotinib versus chemotherapy in advanced ALK-positive lung cancer","route":"/key-papers/paper-alk-nsclc-n-engl-j-med-2013/"},{"id":"paper-shaw-crown-lorlatinib-crizotinib-nejm-2020","kind":"paper","name":"First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer","route":"/key-papers/paper-shaw-crown-lorlatinib-crizotinib-nejm-2020/"},{"id":"paper-soda-eml4-alk-fusion-nature-2007","kind":"paper","name":"Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer","route":"/key-papers/paper-soda-eml4-alk-fusion-nature-2007/"}],"cancer":[{"id":"alk-positive-nsclc","kind":"cancer","name":"ALK-positive non-small-cell lung cancer","route":"/cancers/alk-positive-nsclc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"section":[{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"term":[{"id":"brain-metastases","kind":"term","name":"Brain metastases (intracranial disease)","route":"/terms/brain-metastases/"},{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"},{"id":"fish","kind":"term","name":"FISH / ISH (in situ hybridisation)","route":"/terms/fish/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"},{"id":"oncogene-addiction","kind":"term","name":"Oncogene addiction","route":"/terms/oncogene-addiction/"}],"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/"},{"id":"met","kind":"target","name":"MET","route":"/targets/met/"}],"drug":[{"id":"crizotinib","kind":"drug","name":"Crizotinib","route":"/drugs/crizotinib/"}],"company":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"institution":[{"id":"mgh","kind":"institution","name":"Massachusetts General Hospital Cancer Center","route":"/institutions/mgh/"}],"person":[{"id":"alice-shaw","kind":"person","name":"Alice T. Shaw","route":"/people/alice-shaw/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-brain-delivery","kind":"bottleneck","name":"The brain: barrier and sanctuary","route":"/bottlenecks/b-brain-delivery/"},{"id":"b-trial-enrolment","kind":"bottleneck","name":"Trials enrol too few, too slowly","route":"/bottlenecks/b-trial-enrolment/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"roadmap":[{"id":"lung-cancer-evidence-roadmap","kind":"roadmap","name":"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","route":"/roadmaps/lung-cancer-evidence-roadmap/"}]}}