VISION
¹⁷⁷Lu-PSMA-617 improved survival in mCRPC, the trial behind Pluvicto
Quick Answer
VISION (Sartor et al., N Engl J Med 2021) was the phase 3 randomized trial that established ¹⁷⁷Lu-PSMA-617 radioligand therapy as a standard treatment for metastatic castration-resistant prostate cancer (mCRPC) after progression on an androgen-receptor pathway inhibitor and a taxane. Adding ¹⁷⁷Lu-PSMA-617 to standard of care improved overall survival and radiographic progression-free survival in PSMA-positive disease, and directly supported the FDA approval of Pluvicto. It is the trial that brought PSMA theranostics into routine oncology.
The trial
Design: open-label phase 3, ~831 patients with PSMA-positive mCRPC (on ⁶⁸Ga-PSMA-11 PET) who had progressed after ≥1 androgen-receptor pathway inhibitor and 1–2 taxane regimens. Randomized 2:1 to ¹⁷⁷Lu-PSMA-617 (7.4 GBq every 6 weeks, up to 6 cycles) plus standard of care versus standard of care alone. Dual primary endpoints: overall survival (OS) and radiographic progression-free survival (rPFS).
Key result
¹⁷⁷Lu-PSMA-617 improved overall survival (~15.3 vs 11.3 months; HR ≈ 0.62) and rPFS (~8.7 vs 3.4 months; HR ≈ 0.40). The most notable toxicities were myelosuppression, dry mouth (xerostomia), fatigue, and nausea — the salivary/marrow uptake being characteristic of PSMA-directed therapy. Patients were selected by PSMA-positive imaging, embedding the theranostic principle (image the target, then treat it).
Why it mattered
VISION was the first phase 3 trial to show a survival benefit for a PSMA-targeted radioligand therapy, and it converted PSMA theranostics from investigational to standard care — underpinning the regulatory approval of ¹⁷⁷Lu-PSMA-617 (Pluvicto) for post-taxane, PSMA-positive mCRPC. It also cemented PSMA PET as the companion diagnostic that selects patients for the therapy.
Context & caveats
VISION enrolled a PSMA-selected, heavily pretreated population; it did not test the therapy earlier in the disease course (later trials — PSMAfore, ENZA-p — address earlier settings). The concept of PSMA-negative/FDG-positive discordant disease that escapes the therapy is a key limitation of patient selection.
Self-Check
Q1. What did VISION establish, and in what population?
Answer: That ¹⁷⁷Lu-PSMA-617 added to standard of care improves OS and rPFS in PSMA-positive mCRPC after an ARPI and a taxane — the basis for Pluvicto's approval.
Q2. What were the approximate survival results?
Answer: OS ~15.3 vs 11.3 months (HR ≈ 0.62) and rPFS ~8.7 vs 3.4 months (HR ≈ 0.40).
Q3. What characteristic toxicities were seen, and why?
Answer: Myelosuppression, xerostomia, fatigue, nausea — dry mouth reflecting physiologic salivary PSMA expression and marrow effects reflecting radioligand dosimetry.
Q4. How were patients selected, and what does that illustrate?
Answer: By PSMA-positive ⁶⁸Ga-PSMA-11 PET — the theranostic principle: image the target to select patients, then treat with the matched radioligand.
Key References
- Sartor O, et al. Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer (VISION). N Engl J Med 2021;385:1091–1103. doi:10.1056/NEJMoa2107322
Evidence & sources
https://nuc.med/vision-trial/ Report an issue