# UpFrontPSMA

Source: https://nuclide.cc/trials/upfront-psma/  
Nuclide record `upfront-psma` (Trial). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

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.

Among 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.

UpFrontPSMA 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.

## Fields

- Kind: Trial
- Status: active
- Last checked: 2026-09-22
- Also known as: ANZUP sequential LuPSMA and docetaxel trial
- Tags: radioligand therapy; prostate cancer; hormone-sensitive; first line
- Registry id: 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
- Enrolled: 130
- 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)
- Outcomes: Undetectable PSA (≤0.2 ng/mL) at 48 weeks: 177Lu-PSMA-617 (2 cycles) then docetaxel (6 cycles) + ADT 41% vs Docetaxel (6 cycles) + ADT alone 16%; PSA progression-free survival: 177Lu-PSMA-617 then docetaxel + ADT 31 months vs Docetaxel + ADT alone 20 months, HR 0.6; Freedom from castration resistance: 177Lu-PSMA-617 then docetaxel + ADT 20 months vs Docetaxel + ADT alone 16 months, HR 0.6; Grade 3-4 treatment-related adverse events: 177Lu-PSMA-617 then docetaxel + ADT 29% vs Docetaxel + ADT alone 27%

## Sources

- Lancet Oncology 2024: UpFrontPSMA primary results (Azad et al.): https://pubmed.ncbi.nlm.nih.gov/39293461/
- ClinicalTrials.gov: NCT04343885: https://clinicaltrials.gov/study/NCT04343885
- ANZUP: UpFrontPSMA trial page: https://anzup.org.au/clinical-trial/upfrontpsma-trial/

## Connected records

- drugs: [Docetaxel](https://nuclide.cc/drugs/docetaxel/), [Lutetium-177 vipivotide tetraxetan](https://nuclide.cc/drugs/pluvicto/)
- indications: [Metastatic hormone-sensitive prostate cancer](https://nuclide.cc/indications/prostate-mhspc/)
- trials: [PSMAddition](https://nuclide.cc/trials/psmaddition/)
- isotopes: [Lutetium-177](https://nuclide.cc/isotopes/lu-177/)

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