{"entity":{"id":"paper-drup-van-der-velden-nature-2019","kind":"paper","name":"The Drug Rediscovery Protocol: approved cancer drugs used outside their licence, inside a national trial","aka":[],"tldr":"The first report of the Dutch DRUP trial: a third of 215 patients with no standard options left benefited from an approved drug matched to their tumour's molecular profile and given outside its licence.","summary":"Large-scale genetic profiling of tumours finds actionable variants for which approved drugs exist, but when patients are treated with those drugs outside their label the successes and failures are not systematically collected or shared. The Drug Rediscovery Protocol is an adaptive precision-oncology trial that treats such patients, who must have exhausted or declined standard therapy, in cohorts defined by tumour type and molecular variant, to find signals of activity.\n\nThe abstract reports an overall clinical benefit rate, defined as complete or partial response or stable disease beyond 16 weeks, of 34 per cent in 215 treated patients, 136 of whom received targeted therapies and 79 immunotherapy. The median duration of clinical benefit was 9 months (95 per cent confidence interval 8 to 11), with 26 patients still benefiting at data cut-off. A cohort of patients with microsatellite-unstable tumours given nivolumab had a clinical benefit rate of 63 per cent, while patients with colorectal cancer with a relatively low mutational load gained only limited benefit from immunotherapy.","asOf":"2026-11-03","links":[{"label":"Nature 2019","url":"https://doi.org/10.1038/s41586-019-1600-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31570881/"}],"tags":[],"related":["paper-priestley-hartwig-metastatic-wgs-nature-2019"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["hartwig-medical-foundation"],"institutions":["nki","oncode-institute"],"pathways":[],"terms":[],"trials":["drup"],"people":["emile-voest","myriam-chalabi"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature","year":2019,"doi":"10.1038/s41586-019-1600-x","pmid":"31570881","authors":"van der Velden DL, Hoes LR, van der Wijngaart H, et al.","paperType":"translational","findings":["Clinical benefit (complete or partial response, or stable disease beyond 16 weeks) in 34% of 215 treated patients.","136 patients received targeted therapies and 79 immunotherapy.","Median duration of clinical benefit 9 months (95% CI 8 to 11).","Clinical benefit rate 63% in a cohort of microsatellite-unstable tumours treated with nivolumab."],"whatItMeans":"It showed that a country can let patients use an approved drug off-label without each case vanishing into an anecdote: every treatment is a trial cohort, and a cohort that works can make the case for paying for that use.","caveats":["Non-randomised cohorts with small numbers each; a benefit signal is not proof of benefit over other options.","Stable disease beyond 16 weeks counts as benefit, which flatters slow-growing tumours.","Drugs are contributed by companies, so the menu is limited to what they offer."],"participants":215},"route":"/key-papers/paper-drup-van-der-velden-nature-2019/","neighbours":{"paper":[{"id":"paper-priestley-hartwig-metastatic-wgs-nature-2019","kind":"paper","name":"Whole-genome sequencing of 2,520 metastatic tumours from the Dutch Hartwig cohort","route":"/key-papers/paper-priestley-hartwig-metastatic-wgs-nature-2019/"}],"company":[{"id":"hartwig-medical-foundation","kind":"company","name":"Hartwig Medical Foundation","route":"/companies/hartwig-medical-foundation/"}],"institution":[{"id":"nki","kind":"institution","name":"Netherlands Cancer Institute (NKI-AvL)","route":"/institutions/nki/"},{"id":"oncode-institute","kind":"institution","name":"Oncode Institute","route":"/institutions/oncode-institute/"}],"trial":[{"id":"drup","kind":"trial","name":"DRUP (Drug Rediscovery Protocol)","route":"/trials/drup/"}],"person":[{"id":"emile-voest","kind":"person","name":"Emile Voest","route":"/people/emile-voest/"},{"id":"myriam-chalabi","kind":"person","name":"Myriam Chalabi","route":"/people/myriam-chalabi/"}]}}