PSMAfore
177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy in taxane-naive patients with progressive metastatic castration-resistant prostate cancer
Phase 3N = 468NCT04689828
- Population
- Taxane-naive men with PSMA-positive metastatic castration-resistant prostate cancer who had progressed once on a previous ARPI; 468 randomised (the registry record lists 469)
- Design
- Open-label, randomised (1:1) phase 3 trial at 74 sites in Europe and North America: intravenous 177Lu-PSMA-617 7.4 GBq every 6 weeks for six cycles versus a change of ARPI (abiraterone or enzalutamide). Crossover from ARPI change to 177Lu-PSMA-617 was allowed after centrally confirmed radiographic progression. The primary endpoint was radiographic progression-free survival in the intention-to-treat population; overall survival was a key secondary endpoint.
- Primary endpoint
- rPFS
- Arms
- 177Lu-PSMA-617 (experimental, n = 234): 177Lu-PSMA-617 7.4 GBq (200 mCi) +/- 10% intravenously every 6 weeks for six cycles
- Change of ARPI (control, n = 234): Abiraterone or enzalutamide, orally and continuously per product labelling
- People
- Morris MJ
rPFSHR 0.41 (95% CI 0.29–0.56)Δ median rPFS+3.75 monthsrPFSHR 0.49 (95% CI 0.39–0.61)Δ median rPFS+6.01 monthsOSHR 0.91 (95% CI 0.72–1.14)Δ median OS+1.35 months
Show the numbers
| Endpoint | Analysis | 177Lu-PSMA-617 | Change of ARPI | Effect |
|---|---|---|---|---|
| rPFSTime from randomisation to radiographic progression or death | primaryMorris 2024 | median 9.3 months | median 5.55 months (4.04–5.95) | HR 0.41 (95% CI 0.29–0.56)P<0.0001Primary analysis at the first data cutoff (166 rPFS events). The 95% CI for the 177Lu-PSMA-617 median is 6.77 to not estimable (upper bound not estimable). Median time from randomisation to the first data cutoff was 7.26 months (the full text gives a median rPFS follow-up of 3.71 vs 2.35 months). |
| rPFSTime from randomisation to radiographic progression or death | long term-updateMorris 2024 | median 11.6 months (9.30–14.19) | median 5.59 months (4.21–5.95) | HR 0.49 (95% CI 0.39–0.61)Updated analysis at the third data cutoff (334 rPFS events); no p-value is given in the abstract. Median time from randomisation to the third data cutoff was 24.11 months (the full text gives a median rPFS follow-up of 8.77 vs 4.27 months). |
| OS | finalFizazi 2025 | median 24.48 months (19.55–28.94) | median 23.13 months (19.61–25.53) | HR 0.91 (95% CI 0.72–1.14)P=0.20141 of 234 patients (60.3%) randomised to ARPI change crossed over (75.4% of those with centrally confirmed radiographic progression). The crossover-adjusted hazard ratio for death by inverse probability of censoring weighting was 0.59 (95% CI 0.38 to 0.91); this is a modelled estimate, not a randomised comparison. |
| Endpoint | Analysis | 177Lu-PSMA-617 | Change of ARPI | Effect |
|---|---|---|---|---|
| rPFSTime from randomisation to radiographic progression or death | primaryMorris 2024 | median 9.3 months | median 5.55 months (4.04–5.95) | HR 0.41 (95% CI 0.29–0.56)P<0.0001Primary analysis at the first data cutoff (166 rPFS events). The 95% CI for the 177Lu-PSMA-617 median is 6.77 to not estimable (upper bound not estimable). Median time from randomisation to the first data cutoff was 7.26 months (the full text gives a median rPFS follow-up of 3.71 vs 2.35 months). |
| rPFSTime from randomisation to radiographic progression or death | long term-updateMorris 2024 | median 11.6 months (9.30–14.19) | median 5.59 months (4.21–5.95) | HR 0.49 (95% CI 0.39–0.61)Updated analysis at the third data cutoff (334 rPFS events); no p-value is given in the abstract. Median time from randomisation to the third data cutoff was 24.11 months (the full text gives a median rPFS follow-up of 8.77 vs 4.27 months). |
| OS | finalFizazi 2025 | median 24.48 months (19.55–28.94) | median 23.13 months (19.61–25.53) | HR 0.91 (95% CI 0.72–1.14)P=0.20141 of 234 patients (60.3%) randomised to ARPI change crossed over (75.4% of those with centrally confirmed radiographic progression). The crossover-adjusted hazard ratio for death by inverse probability of censoring weighting was 0.59 (95% CI 0.38 to 0.91); this is a modelled estimate, not a randomised comparison. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| rPFS | 0.41 | 0.29–0.56 |
| rPFS | 0.49 | 0.39–0.61 |
| OS | 0.91 | 0.72–1.14 |
- 177Lu-PSMA-617 (experimental)
- Change of ARPI (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | 177Lu-PSMA-617 | Change of ARPI |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 6 | 63.9% | 47.3% |
| 12 | 40.9% | 22.3% |
| 17 | 28.2% | 12.0% |
| 23 | 18.0% | 5.7% |
- 177Lu-PSMA-617 (experimental)
- Change of ARPI (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | 177Lu-PSMA-617 | Change of ARPI |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 7 | 65.8% | 42.0% |
| 15 | 40.8% | 15.6% |
| 22 | 26.9% | 6.5% |
| 29 | 17.7% | 2.7% |
Appears in
Sources
Morris MJ, Castellano D, Herrmann K, de Bono JS, Shore ND, Chi KN, et al. (177)Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial. Lancet. 2024;404(10459):1227-1239.
Fizazi K, Chi KN, Shore ND, Herrmann K, de Bono JS, Castellano D, et al. Final overall survival and safety analyses of the phase III PSMAfore trial of [(177)Lu]Lu-PSMA-617 versus change of androgen receptor pathway inhibitor in taxane-naive patients with metastatic castration-resistant prostate cancer. Ann Oncol. 2025;36(11):1319-1330.