VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer
A radioactive drug that homes to the PSMA protein on prostate cancer cells helped men with heavily pretreated metastatic prostate cancer live about four months longer, launching radioligand therapy as a mainstream treatment.
Overview
Open-label phase 3 trial of 831 men with PSMA-PET-positive metastatic castration-resistant prostate cancer previously treated with at least one androgen-receptor pathway inhibitor and one or two taxanes, randomised 2:1 to 177Lu-PSMA-617 (7.4 GBq every six weeks for up to six cycles) plus protocol-permitted standard care, or standard care alone. Primary endpoints were radiographic PFS and OS.
Median OS was 15.3 vs 11.3 months (HR 0.62) and median rPFS 8.7 vs 3.4 months (HR 0.40). It led to FDA and EMA approval of Pluvicto in 2022, the first radioligand therapy to show a survival benefit in a common cancer, and made PSMA PET a theranostic gatekeeper.
- Median overall survival 15.3 vs 11.3 months; HR 0.62 (95% CI 0.52-0.74).
- Median radiographic PFS 8.7 vs 3.4 months; HR 0.40 (99.2% CI 0.29-0.57).
- PSA decline of 50% or more in 46% vs 7%; objective response in measurable disease 30% vs 2%.
- Grade 3 or higher adverse events 53% vs 38%, mainly anaemia, thrombocytopenia and fatigue; dry mouth was common but rarely severe.
- About 13% of screened patients were excluded by PSMA PET (PSMA-negative lesions), and early dropout in the control arm required protocol changes.
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).
- Standard care in the control arm excluded chemotherapy, radium-223 and other active drugs, and about 56% of control patients withdrew early, weakening the comparison.
- Open-label; the OS benefit is nonetheless robust to sensitivity analyses.
- Requires nuclear medicine infrastructure, isotope supply and PSMA PET access, which are unequally distributed.
- PSMAfore in the pre-chemotherapy setting improved rPFS but not OS, because most control patients crossed over.
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