{"entity":{"id":"comet-1","kind":"trial","name":"COMET-1","aka":["COMET-1","XL184-307","cabozantinib in previously treated mCRPC"],"tldr":"A drug that made bone scans look dramatically better did not make men live longer. It is the best illustration in prostate cancer that a bone scan is not the disease.","summary":"Cabozantinib inhibits MET and vascular endothelial growth factor receptors, and in phase 2 it produced bone scan resolutions in men with castration-resistant prostate cancer that were unlike anything the field had seen. COMET-1 tested whether that translated.\n\nIt randomised 1,028 heavily pretreated men 2:1 to cabozantinib 60 mg daily (682) or prednisone 5 mg twice daily (346). Median overall survival was 11.0 months with cabozantinib and 9.8 months with prednisone, hazard ratio 0.90 (95 percent confidence interval 0.76 to 1.06, stratified log-rank p=0.213). The primary endpoint was not met.\n\nBone scan response at week 12 favoured cabozantinib overwhelmingly, 42 against 3 percent (stratified Cochran-Mantel-Haenszel p<0.001), and radiographic progression-free survival was 5.6 against 2.8 months, hazard ratio 0.48 (0.40 to 0.57, p<0.001). Circulating tumour cell conversion, bone biomarkers and symptomatic skeletal events all improved. PSA outcomes did not.\n\nGrade 3 to 4 adverse events occurred in 71 percent with cabozantinib against 56 percent, and discontinuation for adverse events in 33 against 12 percent. The companion trial COMET-2, in men with bone pain, was also negative. Exelixis stopped developing cabozantinib in prostate cancer.\n\nThe dissociation between the bone scan and survival is the reason bone scan response is not accepted as a registrational endpoint. Cabozantinib changes what the isotope does in bone; it does not change what the cancer does to the man.","status":"negative","asOf":"2026-09-25","links":[{"label":"ClinicalTrials.gov NCT01605227","url":"https://clinicaltrials.gov/study/NCT01605227"},{"label":"COMET-1 (Journal of Clinical Oncology 2016)","url":"https://doi.org/10.1200/JCO.2015.65.5597"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["antiangiogenic"],"targets":["met"],"drugs":["cabozantinib","prednisone"],"companies":["exelixis"],"institutions":[],"pathways":[],"terms":["bone-metastases","castration-resistance"],"trials":["calgb-90401","tasquinimod-10tasq10"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT01605227","phase":"3","setting":"Metastatic castration-resistant prostate cancer progressing after docetaxel and abiraterone or enzalutamide: cabozantinib 60 mg once daily against prednisone 5 mg twice daily, randomised 2:1, with overall survival as the primary endpoint and bone scan response at week 12 as the secondary endpoint","sponsor":"Exelixis","result":"Median overall survival 11.0 against 9.8 months (hazard ratio 0.90, 95 percent confidence interval 0.76 to 1.06, p=0.213): not met. Bone scan response at 12 weeks 42 against 3 percent and radiographic progression-free survival 5.6 against 2.8 months.","yearReported":2016,"enrolled":1028,"enrolledBasis":"randomised","enrolledNote":"1,028 men were randomly assigned at a ratio of two to one, 682 to cabozantinib and 346 to prednisone.","outcomes":[{"endpoint":"Overall survival (median)","primary":true,"unit":"months","arms":[{"name":"Cabozantinib 60 mg daily","n":682,"value":11},{"name":"Prednisone 5 mg twice daily","n":346,"value":9.8}],"hr":0.9,"ci":[0.76,1.06],"p":"0.213","source":"https://doi.org/10.1200/JCO.2015.65.5597"},{"endpoint":"Bone scan response at week 12","unit":"%","arms":[{"name":"Cabozantinib 60 mg daily","n":682,"value":42},{"name":"Prednisone 5 mg twice daily","n":346,"value":3}],"p":"<0.001","source":"https://doi.org/10.1200/JCO.2015.65.5597"},{"endpoint":"Radiographic progression-free survival (median)","unit":"months","arms":[{"name":"Cabozantinib 60 mg daily","n":682,"value":5.6},{"name":"Prednisone 5 mg twice daily","n":346,"value":2.8}],"hr":0.48,"ci":[0.4,0.57],"p":"<0.001","source":"https://doi.org/10.1200/JCO.2015.65.5597"}],"replication":"COMET-2, in men with moderate to severe bone pain, was also negative; CALGB 90401 with bevacizumab produced the same pattern of better progression-free survival and no survival benefit with a different anti-angiogenic."},"route":"/trials/comet-1/","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":"antiangiogenic","kind":"technology","name":"Anti-angiogenic therapy","route":"/technologies/antiangiogenic/"}],"target":[{"id":"met","kind":"target","name":"MET","route":"/targets/met/"}],"drug":[{"id":"cabozantinib","kind":"drug","name":"Cabozantinib","route":"/drugs/cabozantinib/"},{"id":"prednisone","kind":"drug","name":"Prednisone","route":"/drugs/prednisone/"}],"company":[{"id":"exelixis","kind":"company","name":"Exelixis","route":"/companies/exelixis/"}],"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/"}],"trial":[{"id":"tasquinimod-10tasq10","kind":"trial","name":"10TASQ10","route":"/trials/tasquinimod-10tasq10/"},{"id":"calgb-90401","kind":"trial","name":"CALGB 90401","route":"/trials/calgb-90401/"},{"id":"ready-dasatinib","kind":"trial","name":"READY","route":"/trials/ready-dasatinib/"}]}}