{"entity":{"id":"swog-s0421-atrasentan","kind":"trial","name":"SWOG S0421","aka":["SWOG S0421","S0421","atrasentan with docetaxel"],"tldr":"Adding an endothelin blocker to chemotherapy changed nothing, not survival, not progression, not pain.","summary":"SWOG S0421 randomised 994 men with metastatic castration-resistant prostate cancer and bone metastases to docetaxel with atrasentan 10 mg daily or placebo for up to 12 cycles, with the option to continue the study drug for up to 52 weeks in the absence of progression. It was halted early for futility at a planned interim analysis in April 2011.\n\nMedian progression-free survival was 9.2 months (95 percent confidence interval 8.5 to 9.9) with atrasentan and 9.1 months (8.4 to 10.2) with placebo, hazard ratio 1.02 (0.89 to 1.16, p=0.81). Median overall survival was 17.8 months (16.4 to 19.8) against 17.6 months (16.4 to 20.1), hazard ratio 1.04 (0.90 to 1.19, p=0.64). Grade 3 or greater toxicity occurred in 278 of 492 men (57 percent) with atrasentan and 294 of 486 (60 percent) with placebo, p=0.22, and three deaths in the atrasentan group and seven in the placebo group were judged possibly or probably due to protocol treatment.\n\nThe separately published patient-reported outcomes reinforce the null: clinically meaningful pain palliation in 44.0 percent with atrasentan against 41.7 percent with placebo (p=0.70), functional status improvement in 28.7 against 24.2 percent (p=0.13), and no difference over time in Brief Pain Inventory worst pain scores (0.13 points, p=0.23).","status":"negative","asOf":"2026-09-25","links":[{"label":"ClinicalTrials.gov NCT00134056","url":"https://clinicaltrials.gov/study/NCT00134056"},{"label":"SWOG S0421 (Lancet Oncology 2013)","url":"https://doi.org/10.1016/S1470-2045(13)70294-8"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":["ednra"],"drugs":["atrasentan","docetaxel"],"companies":["swog","abbvie"],"institutions":[],"pathways":[],"terms":["bone-metastases","castration-resistance","qol-pro"],"trials":["enthuse-m1-zibotentan","tax-327"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00134056","phase":"3","setting":"Metastatic castration-resistant prostate cancer with bone metastases, stratified by progression type, baseline pain, extraskeletal metastases and bisphosphonate use: docetaxel 75 mg/m2 every 21 days with atrasentan 10 mg daily or placebo for up to 12 cycles, with co-primary endpoints of progression-free survival and overall survival","sponsor":"SWOG Cancer Research Network, funded by the National Cancer Institute with Sanofi-Aventis and Abbott Laboratories","result":"Median overall survival 17.8 against 17.6 months (hazard ratio 1.04, 95 percent confidence interval 0.90 to 1.19) and progression-free survival 9.2 against 9.1 months (1.02, 0.89 to 1.16); halted early for futility, and no difference in pain palliation.","yearReported":2013,"enrolled":994,"enrolledBasis":"randomised","enrolledNote":"994 men were randomly assigned, 498 to atrasentan and 496 to placebo; the trial was halted early for futility in April 2011.","outcomes":[{"endpoint":"Overall survival (median)","primary":true,"unit":"months","arms":[{"name":"Docetaxel with atrasentan","n":498,"value":17.8},{"name":"Docetaxel with placebo","n":496,"value":17.6}],"hr":1.04,"ci":[0.9,1.19],"p":"0.64","source":"https://doi.org/10.1016/S1470-2045(13)70294-8"},{"endpoint":"Progression-free survival (median)","primary":true,"unit":"months","arms":[{"name":"Docetaxel with atrasentan","n":498,"value":9.2},{"name":"Docetaxel with placebo","n":496,"value":9.1}],"hr":1.02,"ci":[0.89,1.16],"p":"0.81","source":"https://doi.org/10.1016/S1470-2045(13)70294-8"}],"replication":"ENTHUSE M1 found the same for zibotentan, the other endothelin A antagonist, in 594 men."},"route":"/trials/swog-s0421-atrasentan/","neighbours":{"cancer":[{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"}],"target":[{"id":"ednra","kind":"target","name":"EDNRA","route":"/targets/ednra/"}],"drug":[{"id":"atrasentan","kind":"drug","name":"Atrasentan","route":"/drugs/atrasentan/"},{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"zibotentan","kind":"drug","name":"Zibotentan","route":"/drugs/zibotentan/"}],"company":[{"id":"abbvie","kind":"company","name":"AbbVie (incl. ImmunoGen, Capstan)","route":"/companies/abbvie/"},{"id":"swog","kind":"company","name":"SWOG Cancer Research Network","route":"/companies/swog/"}],"term":[{"id":"bone-metastases","kind":"term","name":"Bone metastases and skeletal-related events","route":"/terms/bone-metastases/"},{"id":"castration-resistance","kind":"term","name":"Castration-resistant prostate cancer (CRPC)","route":"/terms/castration-resistance/"},{"id":"prostate-failed-programmes","kind":"term","name":"Prostate cancer programmes that failed, and what each failure taught","route":"/terms/prostate-failed-programmes/"},{"id":"qol-pro","kind":"term","name":"Quality of life and patient-reported outcomes (QoL, PRO)","route":"/terms/qol-pro/"}],"trial":[{"id":"enthuse-m1-zibotentan","kind":"trial","name":"ENTHUSE M1","route":"/trials/enthuse-m1-zibotentan/"},{"id":"ready-dasatinib","kind":"trial","name":"READY","route":"/trials/ready-dasatinib/"},{"id":"tax-327","kind":"trial","name":"TAX 327","route":"/trials/tax-327/"}]}}