{"entity":{"id":"triton3","kind":"trial","name":"TRITON3","aka":["TRITON3","rucaparib in BRCA or ATM altered mCRPC"],"tldr":"A PARP inhibitor works for men whose prostate cancer carries a BRCA fault, and does not work for men whose fault is in ATM. Which gene is broken decides whether the drug helps.","summary":"TRITON3 is the cleanest demonstration in prostate cancer that homologous recombination repair is not one thing. Of 4,855 men prescreened or screened, 405 were randomised 2:1 to rucaparib 600 mg twice daily (270) or physician's choice of docetaxel or a second androgen receptor pathway inhibitor (135). Of these, 201 and 101 had a BRCA alteration.\n\nAt 62 months, imaging-based progression-free survival was significantly longer with rucaparib in the BRCA subgroup, median 11.2 against 6.4 months, hazard ratio 0.50 (95 percent confidence interval 0.36 to 0.69), and in the intention-to-treat population, 10.2 against 6.4 months, hazard ratio 0.61 (0.47 to 0.80), p<0.001 for both.\n\nIn the exploratory ATM subgroup, median imaging-based progression-free survival was 8.1 months with rucaparib and 6.8 months with control, hazard ratio 0.95 (0.59 to 1.52). That is no effect. ATM is routinely counted as a homologous recombination repair gene on panel reports, and TRITON3 is the evidence that counting it that way over-promises.\n\nThe most frequent adverse events with rucaparib were fatigue and nausea. The screening ratio, 4,855 to 405, is worth quoting to any man being offered genomic testing: the eligible genotype is uncommon, and a negative result is the usual result.","status":"mixed","asOf":"2026-09-25","links":[{"label":"ClinicalTrials.gov NCT02975934","url":"https://clinicaltrials.gov/study/NCT02975934"},{"label":"TRITON3 (New England Journal of Medicine 2023)","url":"https://doi.org/10.1056/NEJMoa2214676"},{"label":"NICE TA887: olaparib for previously treated BRCA mutation-positive hormone-relapsed metastatic prostate cancer","url":"https://www.nice.org.uk/guidance/ta887"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["parp-inhibitor","germline-testing"],"targets":["brca","atm","parp"],"drugs":["rucaparib"],"companies":["clovis-oncology"],"institutions":[],"pathways":[],"terms":["hrd","castration-resistance"],"trials":["profound","propel","magnitude","talapro-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02975934","phase":"3","setting":"Metastatic castration-resistant prostate cancer with a BRCA1, BRCA2 or ATM alteration and progression after a second-generation androgen receptor pathway inhibitor: rucaparib 600 mg twice daily against physician's choice of docetaxel or a second androgen receptor pathway inhibitor, randomised 2:1, with imaging-based progression-free survival by independent review as the primary outcome","sponsor":"Clovis Oncology","result":"Median imaging-based progression-free survival 11.2 against 6.4 months in the BRCA subgroup (hazard ratio 0.50, 95 percent confidence interval 0.36 to 0.69) and 10.2 against 6.4 months overall (0.61, 0.47 to 0.80); no effect in the ATM subgroup (0.95, 0.59 to 1.52).","yearReported":2023,"enrolled":405,"enrolledBasis":"randomised","enrolledNote":"4,855 men were prescreened or screened to randomise 405; the screening figure is the one that shows how rare the eligible genotype is.","outcomes":[{"endpoint":"Imaging-based progression-free survival, BRCA subgroup (median)","primary":true,"unit":"months","arms":[{"name":"Rucaparib 600 mg twice daily","n":201,"value":11.2},{"name":"Physician's choice","n":101,"value":6.4}],"hr":0.5,"ci":[0.36,0.69],"p":"<0.001","source":"https://doi.org/10.1056/NEJMoa2214676"},{"endpoint":"Imaging-based progression-free survival, intention to treat (median)","unit":"months","arms":[{"name":"Rucaparib 600 mg twice daily","n":270,"value":10.2},{"name":"Physician's choice","n":135,"value":6.4}],"hr":0.61,"ci":[0.47,0.8],"p":"<0.001","source":"https://doi.org/10.1056/NEJMoa2214676"},{"endpoint":"Imaging-based progression-free survival, ATM subgroup (median)","unit":"months","arms":[{"name":"Rucaparib 600 mg twice daily","value":8.1,"note":"Exploratory analysis; no benefit."},{"name":"Physician's choice","value":6.8}],"hr":0.95,"ci":[0.59,1.52],"source":"https://doi.org/10.1056/NEJMoa2214676"}],"replication":"PROfound found the same gene-dependence, with a larger effect in BRCA1, BRCA2 and ATM combined than in the wider homologous recombination repair panel; PROpel, MAGNITUDE and TALAPRO-2 tested PARP inhibitors with an androgen receptor pathway inhibitor in the first line."},"route":"/trials/triton3/","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":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"},{"id":"parp-inhibitor","kind":"technology","name":"PARP inhibitors","route":"/technologies/parp-inhibitor/"}],"target":[{"id":"atm","kind":"target","name":"ATM","route":"/targets/atm/"},{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"},{"id":"parp","kind":"target","name":"PARP","route":"/targets/parp/"}],"drug":[{"id":"rucaparib","kind":"drug","name":"Rucaparib","route":"/drugs/rucaparib/"}],"company":[{"id":"clovis-oncology","kind":"company","name":"Clovis Oncology","route":"/companies/clovis-oncology/"}],"term":[{"id":"castration-resistance","kind":"term","name":"Castration-resistant prostate cancer (CRPC)","route":"/terms/castration-resistance/"},{"id":"hrd","kind":"term","name":"Homologous recombination deficiency (HRD)","route":"/terms/hrd/"},{"id":"prostate-crpc-sequencing","kind":"term","name":"What follows what in castration-resistant prostate cancer","route":"/terms/prostate-crpc-sequencing/"},{"id":"prostate-hrr-eligibility","kind":"term","name":"Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters","route":"/terms/prostate-hrr-eligibility/"}],"trial":[{"id":"magnitude","kind":"trial","name":"MAGNITUDE","route":"/trials/magnitude/"},{"id":"profound","kind":"trial","name":"PROfound","route":"/trials/profound/"},{"id":"propel","kind":"trial","name":"PROpel","route":"/trials/propel/"},{"id":"talapro-2","kind":"trial","name":"TALAPRO-2","route":"/trials/talapro-2/"}]}}