ENZA-p
Adding the radioactive drug lutetium-PSMA to the hormone drug enzalutamide, with the dose adjusted according to a mid-treatment PET scan, kept prostate cancer under control for longer and helped men with high-risk metastatic disease live longer than enzalutamide on its own.
Overview
ENZA-p (ANZUP 1901) was an open-label, randomised, controlled phase 2 trial at 15 Australian hospitals in men with metastatic castration-resistant prostate cancer who had not yet received docetaxel or an androgen receptor pathway inhibitor for mCRPC, had PSMA-PET-positive disease, and carried at least two risk factors for early progression on enzalutamide. Patients received oral enzalutamide alone or with adaptive-dosed intravenous 177Lu-PSMA-617 (two or four cycles of 7.5 GBq every 6-8 weeks, guided by an interim PSMA PET-CT at week 12). The primary endpoint was PSA progression-free survival.
Among 162 randomised patients, adding LuPSMA improved PSA progression-free survival (13.0 vs 7.8 months, HR 0.43, p<0.0001) and PSA response rate (93% vs 68%) at the interim analysis. At longer follow-up (median 34 months), overall survival also favoured the combination (median 34 vs 26 months, HR 0.55, p=0.0053), along with better quality-of-life deterioration-free survival for physical function and overall health. Grade 3-5 adverse events were comparable between arms, with anaemia and thrombocytopenia occurring only in the combination group; there were no treatment-related deaths.
ENZA-p is the first randomised trial to show an overall survival benefit for adding LuPSMA to an ARPI ahead of chemotherapy, using biomarker-guided adaptive dosing via interim PSMA PET, and it has prompted phase 3 evaluation of the same combination strategy.
- Median 13 vs 7.8 months with Enzalutamide + adaptive-dosed 177Lu-PSMA-617 compared with Enzalutamide alone; about 5.2 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 57 percent lower chance of the event at any given time (hazard ratio 0.43, likely range 0.29 to 0.63).
- 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 34 vs 26 months with Enzalutamide + adaptive-dosed 177Lu-PSMA-617 compared with Enzalutamide alone; about 8 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 45 percent lower chance of the event at any given time (hazard ratio 0.55, likely range 0.36 to 0.84).
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- 93 vs 68 out of 100 had their tumour shrink with Enzalutamide + 177Lu-PSMA-617 compared with Enzalutamide 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.
- A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.
- 46 vs 44 out of 100 reached this endpoint with Enzalutamide + 177Lu-PSMA-617 compared with Enzalutamide 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: Metastatic castration-resistant prostate cancer, PSMA-PET-positive, no prior docetaxel or ARPI for mCRPC, with at least two risk factors for early progression on enzalutamide; first-line mCRPC. People in a different situation may not see the same effect.
- The trial selected people by a biomarker (PSMA); the result should not be assumed for people whose cancer does not have it.
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.
162 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| PSA progression-free survivalprimary | Enzalutamide + adaptive-dosed 177Lu-PSMA-617 | 83 | 13 months | 0.43 (0.29 to 0.63) | <0.0001 | link |
| Enzalutamide alone | 79 | 7.8 months | ||||
| Overall survival (longer follow-up) | Enzalutamide + adaptive-dosed 177Lu-PSMA-617 | 83 | 34 months | 0.55 (0.36 to 0.84) | 0.0053 | link |
| Enzalutamide alone | 79 | 26 months | ||||
| PSA response rate (≥50% decline) | Enzalutamide + 177Lu-PSMA-617 | 83 | 93% | - | - | - |
| Enzalutamide alone | 79 | 68% | ||||
| Grade 3-5 adverse events (secondary-outcomes report) | Enzalutamide + 177Lu-PSMA-617 | 81 | 46% | - | - | link |
| Enzalutamide alone | 79 | 44% |
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