{"entity":{"id":"paper-therap-lancet-2021","kind":"paper","name":"TheraP: [177Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer","aka":[],"tldr":"In men whose prostate cancer had grown after chemotherapy, a radioactive drug that homes in on prostate cancer cells (lutetium-177 PSMA-617) shrank the PSA marker in more men, and caused fewer serious side effects, than the standard chemotherapy drug it was compared with.","summary":"TheraP (ANZUP 1603) was an open-label, randomised phase 2 trial at 11 Australian centres. Men with metastatic castration-resistant prostate cancer progressing after docetaxel, selected by centrally reviewed 68Ga-PSMA-11 and FDG PET/CT (excluding FDG-positive/PSMA-negative discordant disease), were randomised 1:1 to [177Lu]Lu-PSMA-617 (6.0-8.5 GBq IV every 6 weeks, up to six cycles) or cabazitaxel (20 mg/m2 IV every 3 weeks, up to ten cycles). The primary endpoint was a PSA50 response.\n\nOf 291 men screened, 200 were PET-eligible and randomised. PSA50 responses were 66% with 177Lu-PSMA-617 versus 37% with cabazitaxel by intention to treat (difference 29 percentage points, 95% CI 16-42, p<0.0001). Grade 3-4 adverse events were less frequent with the radioligand (33% versus 53%). A mature follow-up analysis (Hofman et al., Lancet Oncology 2024) found overall survival was similar between arms (restricted mean survival time 19.1 versus 19.6 months), with substantial crossover (32% of the radioligand-therapy group and 20% of the cabazitaxel group went on to the other treatment).\n\nTheraP was the first randomised trial to compare a PSMA radioligand head-to-head against a standard chemotherapy and used PET-based patient selection prospectively, a design later echoed by VISION and PSMAfore. It helped establish 177Lu-PSMA-617 (subsequently approved as Pluvicto) as a credible alternative to cabazitaxel in the post-docetaxel setting.","asOf":"2026-09-22","links":[{"label":"PubMed: TheraP primary results (Lancet 2021)","url":"https://pubmed.ncbi.nlm.nih.gov/33581798/"},{"label":"PubMed: TheraP overall survival (Lancet Oncol 2024)","url":"https://pubmed.ncbi.nlm.nih.gov/38043558/"}],"tags":["prostate cancer","radioligand therapy","randomised trial"],"related":["therap","vision","lu177-radioligand-therapy","pluvicto","psma-pet","cabazitaxel","prostate-mcrpc","michael-morris","hofman-michael","louise-emmett","sandhu-shahneen","ga-68","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Lancet","year":2021,"doi":"10.1016/S0140-6736(21)00237-3","pmid":"33581798","authors":"Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, et al.","paperType":"rct","findings":["PSA50 response: 66% (177Lu-PSMA-617) vs 37% (cabazitaxel) by intention to treat; difference 29% (95% CI 16-42), p<0.0001.","Grade 3-4 adverse events: 33% (98 men, PSMA arm) vs 53% (85 men, cabazitaxel arm); no deaths attributed to 177Lu-PSMA-617.","Mature follow-up (median 35.7 months): overall survival restricted mean survival time 19.1 months (PSMA) vs 19.6 months (cabazitaxel), difference -0.5 months (95% CI -3.7 to 2.7), p=0.77 - no evidence of an OS difference.","80 of 291 registered men (27%) were excluded after PET screening for low PSMA expression or FDG-discordant disease; their median survival was substantially shorter (RMST 11.0 months)."],"whatItMeans":"For men whose prostate cancer has grown after chemotherapy, a PSMA-targeted radioactive treatment worked at least as well as, and was gentler than, the chemotherapy drug it replaced - provided a PET scan first confirms the cancer takes up the PSMA tracer.","caveats":["Phase 2, single-country (Australia), open-label, not powered for overall survival as a primary endpoint.","High crossover between arms after the randomised period complicates the survival comparison.","PET-based selection excluded over a quarter of screened men, whose prognosis was worse regardless of treatment - the trial says nothing about that PSMA-negative group."],"changedPractice":true,"participants":200},"route":"/key-papers/paper-therap-lancet-2021/","neighbours":{"trial":[{"id":"therap","kind":"trial","name":"TheraP (ANZUP 1603)","route":"/trials/therap/"},{"id":"vision","kind":"trial","name":"VISION","route":"/trials/vision/"}],"technology":[{"id":"lu177-radioligand-therapy","kind":"technology","name":"Lutetium-177 radioligand therapy","route":"/technologies/lu177-radioligand-therapy/"},{"id":"psma-pet","kind":"technology","name":"PSMA PET","route":"/technologies/psma-pet/"}],"drug":[{"id":"cabazitaxel","kind":"drug","name":"Cabazitaxel","route":"/drugs/cabazitaxel/"},{"id":"pluvicto","kind":"drug","name":"Lutetium-177 vipivotide tetraxetan","route":"/drugs/pluvicto/"}],"indication":[{"id":"prostate-mcrpc","kind":"indication","name":"Metastatic castration-resistant prostate cancer","route":"/indications/prostate-mcrpc/"}],"person":[{"id":"louise-emmett","kind":"person","name":"Louise Emmett","route":"/people/louise-emmett/"},{"id":"hofman-michael","kind":"person","name":"Michael Hofman","route":"/people/hofman-michael/"},{"id":"michael-morris","kind":"person","name":"Michael J. Morris","route":"/people/michael-morris/"},{"id":"sandhu-shahneen","kind":"person","name":"Shahneen Sandhu","route":"/people/sandhu-shahneen/"}],"isotope":[{"id":"ga-68","kind":"isotope","name":"Gallium-68","route":"/isotopes/ga-68/"},{"id":"lu-177","kind":"isotope","name":"Lutetium-177","route":"/isotopes/lu-177/"}]}}