Overview
PSMAfore, trial NCT04689828 sponsored by Novartis and published in the Lancet in 2024, moved Pluvicto, or 177Lu-PSMA-617, before chemotherapy in PSMA-positive metastatic castration-resistant prostate cancer after one androgen receptor pathway inhibitor. It randomised 468 taxane-naive men to the radioligand or a switch of androgen receptor pathway inhibitor, met its primary radiographic progression-free survival endpoint with a large effect, and overall survival was confounded by crossover of most control patients, with crossover-adjusted analyses favouring the radioligand; approval in the pre-chemotherapy setting followed in 2025. Whether earlier use improves survival, not just progression, is the open question.
- Median 12 vs 5.6 months with 177Lu-PSMA-617 compared with ARPI switch; about 6.4 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 59 percent lower chance of the event at any given time (hazard ratio 0.41, likely range 0.29 to 0.56).
- 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.
- The treated group had about 41 percent lower chance of the event at any given time (hazard ratio 0.59).
- The absolute difference, how many more people out of 100 were helped, is not reported here.
- Unadjusted OS HR 0.98 with 84% crossover from control
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- Unadjusted OS HR 0.98 with 84% crossover from control.
- These results apply to the people the trial enrolled: PSMA+ mCRPC after one ARPI, taxane-naive: 177Lu-PSMA-617 vs ARPI switch. 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.
469 enrolled.
Unadjusted OS HR 0.98 with 84% crossover from control
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Radiographic progression-free survivalprimary | 177Lu-PSMA-617 | 234 | 12 months | 0.41 (0.29 to 0.56) | <0.0001 | link |
| ARPI switch | 234 | 5.6 months | ||||
| Overall survival (crossover-adjusted) | 177Lu-PSMA-617 | - | Unadjusted OS HR 0.98 with 84% crossover from control | 0.59 | - | link |
| ARPI switch | - | - |
For men who still have a working hormone treatment option but whose cancer is progressing, offering the PSMA radioligand therapy sooner - before chemotherapy - delayed disease progression, though it did not clearly extend how long men lived once the very high rate of patients switching over is accounted for.
Men with metastatic castration-resistant prostate cancer that has progressed after hormonal therapy and chemotherapy, and whose tumours show PSMA on a PET scan, can now receive lutetium-PSMA, which extends life, controls pain and is usually better tolerated than further chemotherapy. It has established a new treatment class in which a scan decides who gets the matching radioactive drug, and it is now being tested earlier in the disease (PSMAfore, PSMAddition).
Similar pages
not linked directly; found by shared links- TrialVISION
Shares Estimands and intercurrent events (ICH E9(R1)), Crossover in trials, Salivary gland toxicity (xerostomia) from PSMA radioligand therapy, mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer).
- TermAndrogen receptor pathway inhibitor (ARPI)
Shares mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer), PSMAfore: 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor in taxane-naive mCRPC, Prostate cancer.
- Agent177Lu-PSMA-I&T
Shares Salivary gland toxicity (xerostomia) from PSMA radioligand therapy, PSMA theranostics roadmap: antigen discovery → PSMA PET → 177Lu-PSMA-617 → earlier lines and alpha, Metastatic castration-resistant prostate cancer, Prostate cancer.
- TrialONC-392 Plus Lutetium Lu 177 Vipivotide Tetraxetan in Patients With mCRPC
Shares Metastatic castration-resistant prostate cancer, Lutetium-177 vipivotide tetraxetan, Prostate cancer, Lutetium-177.
- PersonKen Herrmann
Shares PSMAfore: 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor in taxane-naive mCRPC, VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer, Lutetium-177 vipivotide tetraxetan, Prostate cancer.
- TrialStudy of Lutetium (177Lu) Vipivotide Tetraxetan in mCRPC Participants With Moderately and Severely Impaired and With Normal Renal Function
Shares Metastatic castration-resistant prostate cancer, Lutetium-177 vipivotide tetraxetan, Prostate cancer, Lutetium-177.
- TrialTheraP (ANZUP 1603)
Shares Crossover in trials, Metastatic castration-resistant prostate cancer, Lutetium-177 vipivotide tetraxetan, Prostate cancer.
- TrialAn Open-label Study of Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in Combination With ARPI Versus AAA617 in PSMA Positive First-line mCRPC
Shares Metastatic castration-resistant prostate cancer, Lutetium-177 vipivotide tetraxetan, Prostate cancer, Lutetium-177.