{"entity":{"id":"affinity-custirsen","kind":"trial","name":"AFFINITY","aka":["AFFINITY","custirsen with cabazitaxel"],"tldr":"The second attempt with the same drug, this time after chemotherapy had already failed once. It also found nothing, including in the men expected to benefit most.","summary":"AFFINITY randomised 635 men whose metastatic castration-resistant prostate cancer had progressed after docetaxel to cabazitaxel and prednisone with or without custirsen, stratified by opioid use for cancer-related pain, radiographic evidence of progression on first-line docetaxel, and previous abiraterone or enzalutamide.\n\nMedian follow-up was 28.3 months in the custirsen group and 29.8 months in the control group. Median overall survival was 14.1 months (95 percent confidence interval 12.7 to 15.9) with custirsen and 13.4 months (12.1 to 14.9) without, hazard ratio 0.95 (0.80 to 1.12, log-rank p=0.53). In the prespecified poor-prognosis subgroup, the co-primary endpoint, it was 11.0 months (9.3 to 13.3) against 10.9 months (8.2 to 12.4), hazard ratio 0.97 (0.80 to 1.21, p=0.80).\n\nThe commonest grade 3 or worse adverse events with custirsen against control were neutropenia (70 of 315 against 61 of 312), anaemia (68 against 49), fatigue (23 against 18), asthenia (16 against 8), bone pain (16 against 5) and febrile neutropenia (16 against 9). Serious adverse events occurred in 155 (49 percent) against 132 (42 percent). Twenty-seven men died within 30 days of treatment in the custirsen group against 17 in the control group.\n\nWith SYNERGY, this ended the clusterin hypothesis as a therapeutic target in prostate cancer.","status":"negative","asOf":"2026-09-25","links":[{"label":"ClinicalTrials.gov NCT01578655","url":"https://clinicaltrials.gov/study/NCT01578655"},{"label":"AFFINITY (Lancet Oncology 2017)","url":"https://doi.org/10.1016/S1470-2045(17)30605-8"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["antisense-sirna","cytotoxic-chemotherapy"],"targets":[],"drugs":["custirsen","cabazitaxel","prednisone"],"companies":["achieve-life-sciences"],"institutions":[],"pathways":[],"terms":["castration-resistance"],"trials":["synergy-custirsen","tropic"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT01578655","phase":"3","setting":"Radiographically documented metastatic castration-resistant prostate cancer progressing after docetaxel, Karnofsky score above 70 percent: cabazitaxel 25 mg/m2 every 21 days with prednisone 10 mg daily, with or without custirsen 640 mg on days 1, 8 and 15 plus three loading doses, for up to ten cycles, with co-primary endpoints of overall survival in all randomised men and in a poor-prognosis subgroup","sponsor":"OncoGenex Technologies","result":"Median overall survival 14.1 against 13.4 months (hazard ratio 0.95, 95 percent confidence interval 0.80 to 1.12) overall, and 11.0 against 10.9 months (0.97, 0.80 to 1.21) in the poor-prognosis subgroup: no benefit on either co-primary endpoint.","yearReported":2017,"enrolled":635,"enrolledBasis":"randomised","enrolledNote":"795 men were screened between 9 September 2012 and 29 September 2014 and 635 were randomised at 95 cancer treatment centres in eight countries.","outcomes":[{"endpoint":"Overall survival, all randomised (median)","primary":true,"unit":"months","arms":[{"name":"Cabazitaxel, prednisone and custirsen","n":317,"value":14.1},{"name":"Cabazitaxel and prednisone","n":318,"value":13.4}],"hr":0.95,"ci":[0.8,1.12],"p":"0.53","source":"https://doi.org/10.1016/S1470-2045(17)30605-8"},{"endpoint":"Overall survival, poor-prognosis subgroup (median)","primary":true,"unit":"months","arms":[{"name":"Cabazitaxel, prednisone and custirsen","value":11},{"name":"Cabazitaxel and prednisone","value":10.9}],"hr":0.97,"ci":[0.8,1.21],"p":"0.80","source":"https://doi.org/10.1016/S1470-2045(17)30605-8"}],"replication":"SYNERGY had already failed with the same drug and first-line docetaxel in 1,022 men."},"route":"/trials/affinity-custirsen/","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/"},{"id":"antisense-sirna","kind":"technology","name":"Oligonucleotide therapeutics","route":"/technologies/antisense-sirna/"}],"drug":[{"id":"cabazitaxel","kind":"drug","name":"Cabazitaxel","route":"/drugs/cabazitaxel/"},{"id":"custirsen","kind":"drug","name":"Custirsen","route":"/drugs/custirsen/"},{"id":"prednisone","kind":"drug","name":"Prednisone","route":"/drugs/prednisone/"}],"company":[{"id":"achieve-life-sciences","kind":"company","name":"Achieve Life Sciences (formerly OncoGenex)","route":"/companies/achieve-life-sciences/"}],"term":[{"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":"synergy-custirsen","kind":"trial","name":"SYNERGY","route":"/trials/synergy-custirsen/"},{"id":"tropic","kind":"trial","name":"TROPIC","route":"/trials/tropic/"}]}}