UpFrontPSMA
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.
Overview
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.
- 41 vs 16 out of 100 reached this endpoint with 177Lu-PSMA-617 (2 cycles) then docetaxel (6 cycles) + ADT compared with Docetaxel (6 cycles) + ADT alone; 25 more per 100.
- Roughly one extra person helped for every 4 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- The p-value (0.0020) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
- This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
- Median 31 vs 20 months with 177Lu-PSMA-617 then docetaxel + ADT compared with Docetaxel + ADT alone; about 11 months longer for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Put another way, the treated group had about 40 percent lower chance of the event at any given time (hazard ratio 0.6, likely range 0.37 to 0.98).
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- Median 20 vs 16 months with 177Lu-PSMA-617 then docetaxel + ADT compared with Docetaxel + ADT alone; about 4 months longer for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Put another way, the treated group had about 40 percent lower chance of the event at any given time (hazard ratio 0.6, likely range 0.38 to 0.96).
- This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
- 29 vs 27 out of 100 reached this endpoint with 177Lu-PSMA-617 then docetaxel + ADT compared with Docetaxel + ADT alone; 2 more per 100.
- On this measure the first group did worse, not better.
- This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
- These results apply to the people the trial enrolled: 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. People in a different situation may not see the same effect.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
130 enrolled.
25/61, 95% CI 30-54 · 10/61, 95% CI 9-28
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Undetectable PSA (≤0.2 ng/mL) at 48 weeksprimary | 177Lu-PSMA-617 (2 cycles) then docetaxel (6 cycles) + ADT | 61 | 41% | - | 0.0020 | link |
| Docetaxel (6 cycles) + ADT alone | 61 | 16% | ||||
| PSA progression-free survival | 177Lu-PSMA-617 then docetaxel + ADT | - | 31 months | 0.6 (0.37 to 0.98) | 0.039 | - |
| Docetaxel + ADT alone | - | 20 months | ||||
| Freedom from castration resistance | 177Lu-PSMA-617 then docetaxel + ADT | - | 20 months | 0.6 (0.38 to 0.96) | 0.033 | - |
| Docetaxel + ADT alone | - | 16 months | ||||
| Grade 3-4 treatment-related adverse events | 177Lu-PSMA-617 then docetaxel + ADT | - | 29% | - | - | link |
| Docetaxel + ADT alone | - | 27% |
Similar pages
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