# PSMAfore

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

## TL;DR

PSMAfore moved Pluvicto before chemotherapy in prostate cancer.

## Summary

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.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-04
- Registry id: NCT04689828
- Phase: 3
- Setting: PSMA+ mCRPC after one ARPI, taxane-naive: 177Lu-PSMA-617 vs ARPI switch
- Sponsor: Novartis
- Enrolled: 469
- Result: rPFS HR 0.41.
- Outcomes: Radiographic progression-free survival: 177Lu-PSMA-617 12 months vs ARPI switch 5.6 months, HR 0.41; Overall survival (crossover-adjusted): 177Lu-PSMA-617 vs ARPI switch, HR 0.59
- Replication: Confirms VISION in the pre-chemotherapy line; SPLASH (177Lu-PSMA-I&T) showed a smaller rPFS effect and no OS benefit, so agent and setting details matter.

## Notes

- PSMAfore moved lutetium-177 PSMA-617 in front of chemotherapy, against a switch of androgen receptor pathway inhibitor. The comparator is the weak point of the design, because CARD had already shown that switching from one androgen receptor pathway inhibitor to the other after rapid failure is much worse than moving to cabazitaxel. There is no NICE recommendation covering the pre-taxane setting in England; NICE TA930, which covers use after taxane chemotherapy and an anti-androgen, does not recommend the drug.

## Sources

- ClinicalTrials.gov NCT04689828: https://clinicaltrials.gov/study/NCT04689828
- NICE TA930: lutetium-177 vipivotide tetraxetan for treating PSMA-positive hormone-relapsed metastatic prostate cancer after 2 or more treatments, not recommended: https://www.nice.org.uk/guidance/ta930

## Connected records

- cancers: [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Radioligand therapy (beta emitters)](https://onco.cc/technologies/radioligand-therapy/)
- drugs: [Lutetium-177 vipivotide tetraxetan](https://onco.cc/drugs/pluvicto/)
- companies: [Novartis](https://onco.cc/companies/novartis/)
- terms: [Crossover in trials](https://onco.cc/terms/crossover/), [Estimands and intercurrent events (ICH E9(R1))](https://onco.cc/terms/estimand/), [mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)](https://onco.cc/terms/mcrpc-mhspc/), [What follows what in castration-resistant prostate cancer](https://onco.cc/terms/prostate-crpc-sequencing/)
- trials: [CARD](https://onco.cc/trials/card/), [TheraP (ANZUP 1603)](https://onco.cc/trials/therap/), [VISION](https://onco.cc/trials/vision/)
- people: [A. Oliver Sartor](https://onco.cc/people/oliver-sartor/), [Michael J. Morris](https://onco.cc/people/michael-morris/)
- key papers: [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](https://onco.cc/key-papers/paper-psmafore-lancet-2024/), [VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer](https://onco.cc/key-papers/paper-vision-nejm-2021/)
- roadmaps: [Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test](https://onco.cc/roadmaps/hormonal-therapy-roadmap/), [Radiopharmaceutical roadmap: iodine → lutetium → actinium](https://onco.cc/roadmaps/radiopharma-roadmap/)
- ideas: [Total-body PET for personalised radioligand dosing](https://onco.cc/ideas/idea-total-body-pet-dosimetry/)

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