177Lu-PSMA-617 in metastatic androgen pathway modulator-sensitive prostate cancer
Mené sur 1 144 patients atteints d'un cancer métastatique hormonosensible de la prostate (âge médian : 68 ans), cet essai randomisé de phase III évalue l'efficacité, du point de vue de la survie sans progression radiographique, la sécurité et la tolérabilité du 177Lu-PSMA-617 en combinaison avec un traitement anti-androgénique et un inhibiteur de la voie du récepteur des androgènes
Lutetium-177 (177Lu)-PSMA-617 is a radioligand therapy that targets prostate-specific membrane antigen (PSMA) and delivers
β-particle radiation to PSMA-expressing cells and the surrounding tumour microenvironment.1 177Lu-PSMA-617 was initially approved in 2022, based on the results of the phase 3 VISION trial1 in patients with PSMA-positive metastatic castration resistant prostate cancer (or metastatic androgen pathway modulator-resistant prostate cancer (APMR) according to the recently updated Prostate Cancer Working Group 4 (PCWG4) nomenclature)2 who had progressed on at least one previous androgen receptor pathway inhibitor (ARPI) and one to two taxanes. The trial showed significant improvement in both radiographic progression-free survival (hazard ratio [HR] 0
·40; 99·2% CI 0·29–0·57; p<0·001) and overall survival (HR 0·62; 95% CI 0·52–0·74; p<0·001) compared with standard of care alone.1 3 years later, in March 2025, 177Lu-PSMA-617 was approved by the US Food and Drug Administration in an earlier metastatic APMR prostate cancer treatment setting based on the phase 3 PSMAfore trial,3 which enrolled patients with PSMA-positive metastatic APMR prostate cancer who had progressed on one previous ARPI without past taxane exposure. In this trial, 177Lu-PSMA-617 significantly improved radiographic progression-free survival compared with ARPI switch (HR 0·49, 95% CI 0·39–0·61).3 Similar to the previous trajectory observed in the treatment landscape of metastatic prostate cancer, where effective agents are progressively moved into earlier lines of therapy, the later PSMAddition trial evaluated 177Lu-PSMA-617 in metastatic hormone-sensitive prostate cancer or metastatic androgen pathway modulator-naive/sensitive (APMN/S) disease in accordance with the updated PCWG4 framework.2
The Lancet , commentaire, 2026