{"entity":{"id":"announce","kind":"trial","name":"ANNOUNCE","aka":[],"tldr":"A PDGFRα antibody that had won accelerated approval on a small trial failed to improve survival in the confirmatory study and was withdrawn.","summary":"ANNOUNCE, trial NCT02451943 sponsored by Eli Lilly and published in JAMA in 2020, tested the PDGFR-alpha antibody olaratumab with doxorubicin against doxorubicin alone as first-line treatment for advanced soft-tissue sarcoma, and found no improvement in survival or progression, so a drug that had won accelerated approval on a small trial was withdrawn in 2019. It randomised 509 patients and showed no difference in overall survival, its primary endpoint. OnCo links it to sarcomas, doxorubicin and William D. Tap. The record treats it as a frequently cited lesson on phase 2 signals and accelerated approval, and why the earlier randomised phase 2 was so misleading remains the open question.","status":"negative","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02451943","url":"https://clinicaltrials.gov/study/NCT02451943"}],"tags":["lesson:accelerated-approval"],"related":[],"cancers":["sarcoma","extremity-soft-tissue-sarcoma"],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["doxorubicin","olaratumab"],"companies":["eli-lilly"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["william-tap"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02451943","phase":"3","setting":"Advanced soft-tissue sarcoma, first line: olaratumab + doxorubicin vs doxorubicin","sponsor":"Eli Lilly","result":"OS HR 1.05 (negative); drug withdrawn.","started":"2015-09-14","startedType":"actual","yearReported":2019,"enrolled":509,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival (median)","primary":true,"unit":"months","arms":[{"name":"Olaratumab + doxorubicin","n":258,"value":20.4},{"name":"Doxorubicin","n":251,"value":19.7}],"hr":1.05,"ci":[0.84,1.3],"source":"https://jamanetwork.com/journals/jama/fullarticle/2763325"}]},"route":"/trials/announce/","neighbours":{"cancer":[{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"},{"id":"extremity-soft-tissue-sarcoma","kind":"cancer","name":"Soft tissue sarcoma of the extremity (localised and advanced)","route":"/cancers/extremity-soft-tissue-sarcoma/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"}],"drug":[{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"olaratumab","kind":"drug","name":"Olaratumab","route":"/drugs/olaratumab/"}],"company":[{"id":"eli-lilly","kind":"company","name":"Eli Lilly (incl. Loxo)","route":"/companies/eli-lilly/"}],"person":[{"id":"william-tap","kind":"person","name":"William D. Tap","route":"/people/william-tap/"}],"term":[{"id":"confirmatory-trial","kind":"term","name":"Confirmatory trial","route":"/terms/confirmatory-trial/"},{"id":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"},{"id":"surrogate-endpoint","kind":"term","name":"Surrogate endpoint","route":"/terms/surrogate-endpoint/"},{"id":"surrogate-validation","kind":"term","name":"Surrogate endpoint validation: which stand-ins have earned trust","route":"/terms/surrogate-validation/"},{"id":"trial-lifecycle","kind":"term","name":"Trial lifecycle: from protocol to label","route":"/terms/trial-lifecycle/"},{"id":"trial-failure-modes","kind":"term","name":"Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover","route":"/terms/trial-failure-modes/"}]}}