{"entity":{"id":"astra","kind":"trial","name":"ASTRA","aka":[],"tldr":"Adding a MEK inhibitor to boost iodine uptake before ablation did not improve complete remission rates, cooling the 'redifferentiation for everyone' idea.","summary":"ASTRA, trial NCT01843062 sponsored by AstraZeneca and reported in 2019, found that adding the MEK inhibitor selumetinib to boost iodine uptake before adjuvant radioiodine in high-risk differentiated thyroid cancer did not improve complete remission rates, cooling the idea of redifferentiation for everyone. It randomised 401 patients to selumetinib or placebo with radioiodine and found no difference in complete remission at eighteen months. OnCo links it to thyroid cancer, radioiodine therapy, kinase inhibitors, the MAPK pathway and the pairing of MAPK inhibitor redifferentiation followed by radioiodine. Redifferentiation remains reserved for selected radioiodine-refractory patients, where small series show MEK or BRAF and MEK inhibitors restore uptake in about half, and whether that selected use can be proved in a randomised trial is the open question.","status":"negative","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT01843062","url":"https://clinicaltrials.gov/study/NCT01843062"},{"label":"JCO 2022","url":"https://ascopubs.org/doi/10.1200/JCO.21.00714"}],"tags":["failure","lesson:adjuvant-vs-active-disease"],"related":[],"cancers":["thyroid"],"sections":[],"technologies":["radioiodine-therapy","kinase-inhibitors"],"targets":[],"drugs":[],"companies":["astrazeneca"],"institutions":[],"pathways":["ras-mapk"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT01843062","phase":"3","setting":"High-risk differentiated thyroid cancer: selumetinib + adjuvant radioiodine vs placebo + radioiodine","sponsor":"AstraZeneca","result":"Complete remission 40% vs 38.5%; not significant.","started":"2013-08-27","startedType":"actual","yearReported":2019,"enrolled":401,"enrolledBasis":"registry","outcomes":[{"endpoint":"Complete remission at 18 months","primary":true,"unit":"%","arms":[{"name":"Selumetinib + RAI","value":40},{"name":"Placebo + RAI","value":38.5}],"source":"https://ascopubs.org/doi/10.1200/JCO.21.00714"}],"replication":"Small redifferentiation series remain positive in refractory patients; the adjuvant setting was negative."},"route":"/trials/astra/","neighbours":{"cancer":[{"id":"thyroid","kind":"cancer","name":"Thyroid cancer","route":"/cancers/thyroid/"}],"technology":[{"id":"radioiodine-therapy","kind":"technology","name":"Radioiodine therapy and whole-body iodine scanning","route":"/technologies/radioiodine-therapy/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"pairing":[{"id":"redifferentiation-rai","kind":"pairing","name":"MAPK inhibitor redifferentiation → radioiodine","route":"/pairings/redifferentiation-rai/"}]}}