{"entity":{"id":"elm-pc-4-orteronel","kind":"trial","name":"ELM-PC 4","aka":["ELM-PC 4","C21004","orteronel in chemotherapy-naive mCRPC"],"tldr":"A cleaner version of abiraterone held the cancer back on scans for five extra months and did not make anyone live longer. It is the clearest warning in prostate cancer that scans are not survival.","summary":"ELM-PC 4 randomised 1,560 chemotherapy-naive men with progressive metastatic castration-resistant prostate cancer to orteronel 400 mg with prednisone twice daily (781) or placebo with prednisone (779), stratified by region and by radiographic disease progression at baseline.\n\nMedian radiographic progression-free survival was 13.8 months (95 percent confidence interval 13.1 to 14.9) with orteronel and 8.7 months (8.3 to 10.9) with placebo, hazard ratio 0.71 (0.63 to 0.80, p<0.0001). After a median 20.7 months, median overall survival was 31.4 months (28.6 to not estimable) against 29.5 months (27.0 to not estimable), hazard ratio 0.92 (0.79 to 1.08, p=0.31).\n\nA 5.1-month improvement in radiographic progression-free survival with no effect on survival is a very large dissociation, and it happened in a trial of 1,560 men with 611 deaths, so it is not a power problem.\n\nToxicity was worse with orteronel: grade 3 or worse increased lipase in 137 of 784 men (17 percent) against 14 of 770 (2 percent), increased amylase in 77 (10 percent) against nine (1 percent), fatigue in 50 (6 percent) against 14 (2 percent) and pulmonary embolism in 40 (5 percent) against 27 (4 percent). Serious adverse events occurred in 358 (46 percent) against 292 (38 percent). Takeda stopped development in this indication on these and the ELM-PC 5 data.","status":"negative","asOf":"2026-09-25","links":[{"label":"ClinicalTrials.gov NCT01193244","url":"https://clinicaltrials.gov/study/NCT01193244"},{"label":"ELM-PC 4 (Lancet Oncology 2015)","url":"https://doi.org/10.1016/S1470-2045(15)70027-6"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["androgen-deprivation"],"targets":["cyp17a1"],"drugs":["orteronel","prednisone"],"companies":["takeda"],"institutions":[],"pathways":[],"terms":["arpi","castration-resistance"],"trials":["cou-aa-302","tasquinimod-10tasq10"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT01193244","phase":"3","setting":"Progressive metastatic castration-resistant prostate cancer with no previous chemotherapy: orteronel 400 mg with prednisone 5 mg twice daily against placebo with prednisone, with two primary endpoints, radiographic progression-free survival and overall survival","sponsor":"Millennium Pharmaceuticals, a subsidiary of Takeda","result":"Median radiographic progression-free survival 13.8 against 8.7 months (hazard ratio 0.71, 95 percent confidence interval 0.63 to 0.80, p<0.0001) but overall survival 31.4 against 29.5 months (0.92, 0.79 to 1.08, p=0.31); development stopped.","yearReported":2015,"enrolled":1560,"enrolledBasis":"randomised","enrolledNote":"2,353 men were assessed for eligibility between 31 October 2010 and 29 June 2012 and 1,560 were randomised at 324 study centres in 43 countries.","outcomes":[{"endpoint":"Radiographic progression-free survival (median)","primary":true,"unit":"months","arms":[{"name":"Orteronel with prednisone","n":781,"value":13.8},{"name":"Placebo with prednisone","n":779,"value":8.7}],"hr":0.71,"ci":[0.63,0.8],"p":"<0.0001","source":"https://doi.org/10.1016/S1470-2045(15)70027-6"},{"endpoint":"Overall survival (median)","primary":true,"unit":"months","arms":[{"name":"Orteronel with prednisone","n":781,"value":31.4},{"name":"Placebo with prednisone","n":779,"value":29.5}],"hr":0.92,"ci":[0.79,1.08],"p":"0.31","source":"https://doi.org/10.1016/S1470-2045(15)70027-6"}],"replication":"ELM-PC 5, the companion trial in men after docetaxel, also missed overall survival; 10TASQ10 with tasquinimod produced the same dissociation between radiographic progression-free survival and survival."},"route":"/trials/elm-pc-4-orteronel/","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":"androgen-deprivation","kind":"technology","name":"Androgen deprivation & AR pathway inhibitors","route":"/technologies/androgen-deprivation/"}],"target":[{"id":"cyp17a1","kind":"target","name":"CYP17A1 (17-alpha-hydroxylase/17,20-lyase)","route":"/targets/cyp17a1/"}],"drug":[{"id":"orteronel","kind":"drug","name":"Orteronel","route":"/drugs/orteronel/"},{"id":"prednisone","kind":"drug","name":"Prednisone","route":"/drugs/prednisone/"}],"company":[{"id":"takeda","kind":"company","name":"Takeda","route":"/companies/takeda/"}],"term":[{"id":"arpi","kind":"term","name":"Androgen receptor pathway inhibitor (ARPI)","route":"/terms/arpi/"},{"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/"}],"trial":[{"id":"tasquinimod-10tasq10","kind":"trial","name":"10TASQ10","route":"/trials/tasquinimod-10tasq10/"},{"id":"cou-aa-302","kind":"trial","name":"COU-AA-302","route":"/trials/cou-aa-302/"}]}}