{"entity":{"id":"upfront-psma","kind":"trial","name":"UpFrontPSMA","aka":["ANZUP sequential LuPSMA and docetaxel trial"],"tldr":"In men newly diagnosed with prostate cancer that has already spread widely, giving two doses of the radioactive drug lutetium-PSMA before starting chemotherapy cleared PSA to undetectable levels in more men than chemotherapy alone, without adding side effects.","summary":"UpFrontPSMA was an investigator-initiated, open-label, randomised phase 2 trial run at 11 Australian hospitals by the Peter MacCallum Cancer Centre and ANZUP, testing 177Lu-PSMA-617 given before docetaxel in men with de novo, high-volume, PSMA-avid metastatic hormone-sensitive prostate cancer starting androgen deprivation therapy. Patients were randomised 1:1 to two cycles of 177Lu-PSMA-617 (7.5 GBq every 6 weeks) followed six weeks later by six cycles of docetaxel, or to six cycles of docetaxel alone, both with continuous ADT. The primary endpoint was the proportion with undetectable PSA (≤0.2 ng/mL) at 48 weeks.\n\nAmong 130 randomised patients (122 evaluable), the LuPSMA-then-docetaxel sequence produced undetectable PSA in 41% versus 16% with docetaxel alone, and improved PSA progression-free survival (31 vs 20 months) and freedom from castration resistance (20 vs 16 months), with grade 3-4 toxicity comparable between arms (29% vs 27%) and no treatment-related deaths.\n\nUpFrontPSMA is the first randomised evidence that adding LuPSMA before chemotherapy can deepen responses in newly diagnosed, high-volume hormone-sensitive disease, a different sequencing strategy from the phase 3 PSMAddition trial (which added LuPSMA to an ARPI rather than to chemotherapy). Overall survival data are still immature; the trial is registered as active, not recruiting, and follow-up continues.","status":"active","asOf":"2026-09-22","links":[{"label":"Lancet Oncology 2024: UpFrontPSMA primary results (Azad et al.)","url":"https://pubmed.ncbi.nlm.nih.gov/39293461/"},{"label":"ClinicalTrials.gov: NCT04343885","url":"https://clinicaltrials.gov/study/NCT04343885"},{"label":"ANZUP: UpFrontPSMA trial page","url":"https://anzup.org.au/clinical-trial/upfrontpsma-trial/"}],"tags":["radioligand therapy","prostate cancer","hormone-sensitive","first line"],"related":["pluvicto","docetaxel","prostate-mhspc","psmaddition","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04343885","phase":"2","setting":"De novo, high-volume metastatic hormone-sensitive prostate cancer, first-line, given within 12 weeks of diagnosis and no more than 4 weeks of androgen deprivation therapy","sponsor":"Peter MacCallum Cancer Centre / ANZUP Cancer Trials Group","result":"41% undetectable PSA at 48 weeks with sequential 177Lu-PSMA-617 then docetaxel vs 16% with docetaxel alone (OR 3.88, 95% CI 1.61-9.38, p=0.002); PSA progression-free survival 31 vs 20 months (HR 0.60, 95% CI 0.37-0.98, p=0.039) (Azad et al., Lancet Oncology 2024)","yearReported":2024,"enrolled":130,"enrolledBasis":"registry","outcomes":[{"endpoint":"Undetectable PSA (≤0.2 ng/mL) at 48 weeks","primary":true,"unit":"%","arms":[{"name":"177Lu-PSMA-617 (2 cycles) then docetaxel (6 cycles) + ADT","n":61,"value":41,"note":"25/61, 95% CI 30-54"},{"name":"Docetaxel (6 cycles) + ADT alone","n":61,"value":16,"note":"10/61, 95% CI 9-28"}],"p":"0.0020","source":"https://pubmed.ncbi.nlm.nih.gov/39293461/"},{"endpoint":"PSA progression-free survival","unit":"months","arms":[{"name":"177Lu-PSMA-617 then docetaxel + ADT","value":31},{"name":"Docetaxel + ADT alone","value":20}],"hr":0.6,"ci":[0.37,0.98],"p":"0.039"},{"endpoint":"Freedom from castration resistance","unit":"months","arms":[{"name":"177Lu-PSMA-617 then docetaxel + ADT","value":20},{"name":"Docetaxel + ADT alone","value":16}],"hr":0.6,"ci":[0.38,0.96],"p":"0.033"},{"endpoint":"Grade 3-4 treatment-related adverse events","unit":"%","arms":[{"name":"177Lu-PSMA-617 then docetaxel + ADT","value":29},{"name":"Docetaxel + ADT alone","value":27}],"source":"https://pubmed.ncbi.nlm.nih.gov/39293461/"}]},"route":"/trials/upfront-psma/","neighbours":{"drug":[{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"pluvicto","kind":"drug","name":"Lutetium-177 vipivotide tetraxetan","route":"/drugs/pluvicto/"}],"indication":[{"id":"prostate-mhspc","kind":"indication","name":"Metastatic hormone-sensitive prostate cancer","route":"/indications/prostate-mhspc/"}],"trial":[{"id":"psmaddition","kind":"trial","name":"PSMAddition","route":"/trials/psmaddition/"}],"isotope":[{"id":"lu-177","kind":"isotope","name":"Lutetium-177","route":"/isotopes/lu-177/"}]}}