PMID-34161051 – VISION Trial Lu-177-PSMA-617 in mCRPC
Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021;385(12):1091-1103.
Quick Reference
| Property | Value |
|---|---|
| PMID | 34161051 |
| DOI | 10.1056/NEJMoa2107322 |
| Year | 2021 |
| Journal | New England Journal of Medicine |
| Study Type | RCT |
| Evidence Level | I |
| Sample | 831 patients with PSMA-positive mCRPC |
| Peptide(s) Studied | Lutetium-177-PSMA-617 |
Key Findings
- Median overall survival was 15.3 months with 177Lu-PSMA-617 + standard of care vs 11.3 months with standard of care alone (HR 0.62; 95% CI 0.52-0.74; p < 0.001)
- Median imaging-based PFS was 8.7 months vs 3.4 months (HR 0.40; p < 0.001)
- PSA response rate (>=50% decline) was 46% vs 7.1%
- Objective response rate among patients with measurable disease was significantly higher with 177Lu-PSMA-617
- Quality of life was maintained or improved with 177Lu-PSMA-617
- Most common grade 3+ AEs: fatigue (5.4%), anemia (12.9%), lymphopenia (7.8%), thrombocytopenia (7.9%)
- Dry mouth was the most common any-grade AE (39%) but was mostly grade 1
Study Design
International, open-label, randomized (2:1), Phase 3 trial (VISION; NCT03511664). Patients with PSMA-positive mCRPC who had previously received at least one androgen-receptor pathway inhibitor and 1-2 taxane regimens were randomized to 177Lu-PSMA-617 (7.4 GBq IV every 6 weeks for 4-6 cycles) plus standard of care, or standard of care alone. Co-primary endpoints: imaging-based PFS and OS. PSMA positivity defined by 68Ga-PSMA-11 PET/CT.
Limitations
- Open-label design
- Standard of care was heterogeneous and did not include novel agents (e.g., PARP inhibitors, next-gen AR inhibitors)
- PSMA-negative patients were excluded; generalizability limited to PSMA-positive population (~87% of screened patients)
- No crossover permitted, which could inflate survival difference
- Predominantly White male population; limited diversity
Clinical Relevance
The VISION trial is the pivotal study that led to FDA approval of 177Lu-PSMA-617 (Pluvicto) in March 2022 for PSMA-positive mCRPC. This represents a paradigm shift in advanced prostate cancer treatment — the first radioligand therapy approved for prostate cancer and the first use of PSMA-targeted therapy in a large Phase 3 trial. The 4-month OS improvement in a heavily pretreated population is clinically meaningful.
Related
#research #RCT #lutetium-177-PSMA-617 #evidence-level-I