Background
Phase III open-label RCT of 831 enrolled (831 randomized; 581 in primary rPFS analysis set) patients with PSMA-positive metastatic castration-resistant prostate cancer on Ga-68 PSMA-11 PET/CT, previously treated with at least one taxane and at least one androgen-receptor pathway inhibitor. Randomized 2:1.
Interventions and follow up
Arm A: 177Lu-PSMA-617 7.4 GBq q6wk (4-6 cycles) plus standard of care
Arm B: Standard of care alone (excluding chemotherapy, radioisotopes, investigational agents)
Primary endpoints: Radiographic PFS and overall survival
Median follow up: 20.9 mo
Arm B: Standard of care alone (excluding chemotherapy, radioisotopes, investigational agents)
Primary endpoints: Radiographic PFS and overall survival
Median follow up: 20.9 mo
Results
Radiographic PFS: 8.7 mo vs 3.4 mo (A vs B); HR 0.40, 99.2% CI 0.29-0.57; P<.001
OS: 15.3 mo vs 11.3 mo (A vs B); HR 0.62, 95% CI 0.52-0.74; P<.001
OS: 15.3 mo vs 11.3 mo (A vs B); HR 0.62, 95% CI 0.52-0.74; P<.001
Adverse events
Grade 3-4 events: 52.7% vs 38.0% (A vs B)
Constitutional/GI: Fatigue 43.1% vs 22.9%; dry mouth 38.8% vs 0.5%; nausea 31.8% vs 13.2%
Musculoskeletal: Back pain 23.4% vs 14.6%; arthralgia 22.3% vs 12.7%
Treatment modifications: Dose reduction 5.7% vs 0%; interruption 16.1% vs 0%; discontinuation 11.9% vs 0%
Constitutional/GI: Fatigue 43.1% vs 22.9%; dry mouth 38.8% vs 0.5%; nausea 31.8% vs 13.2%
Musculoskeletal: Back pain 23.4% vs 14.6%; arthralgia 22.3% vs 12.7%
Treatment modifications: Dose reduction 5.7% vs 0%; interruption 16.1% vs 0%; discontinuation 11.9% vs 0%
Conclusions
177Lu-PSMA-617 added to standard of care significantly prolonged radiographic PFS and overall survival in heavily pretreated PSMA-positive mCRPC.
Key Limitations
High early dropout in the control arm (study withdrawal 56% vs 1.2% before mitigation; improved to 16.3% vs 4.2% after education measures) confounded interpretation and drew criticism that the comparator was undertreated. Standard of care excluded chemotherapy, limiting comparison to active regimens.
Clinical Context
VISION led to FDA (2022) and EMA approval of 177Lu-PSMA-617 (lutetium Lu 177 vipivotide tetraxetan) for PSMA-positive mCRPC previously treated with an androgen-receptor pathway inhibitor and taxane chemotherapy; it is an ASCO/ESMO-recognized option. Subsequent PSMAfore evaluated the agent in the pre-taxane setting.