VISION Trial Eligibility and Treatment Regimen in mCRPC
The VISION trial enrolled 831 men with PSMA-positive metastatic castration-resistant prostate cancer who had previously received at least one androgen receptor pathway inhibitor (ARPI) and one or two taxane-based chemotherapy regimens, randomizing them 2:1 to receive lutetium-177-PSMA-617 (7.4 GBq every 6 weeks for 4-6 cycles) plus standard of care versus standard of care alone. 1, 2
Key Eligibility Criteria
Prior Treatment Requirements
- At least one prior ARPI (abiraterone or enzalutamide) 3
- One or two prior taxane-based chemotherapy regimens (typically docetaxel) 1, 4
- Castrate testosterone levels maintained (medical or surgical castration) 2
PSMA PET/CT Imaging Requirements
The imaging criteria were highly specific and represent a critical selection factor:
- At least one PSMA-positive lesion with Ga-68 PSMA-11 uptake greater than normal liver 3
- No PSMA-negative dominant lesions meeting size criteria 1
PSMA-negative lesions were defined as:
- Bone lesions with soft tissue component ≥1.0 cm
- Lymph nodes ≥2.5 cm in short axis
- Solid organ metastases ≥1.0 cm
- All lacking PSMA uptake (uptake ≤ normal liver) 3
Critical pitfall: Patients were excluded if any single lesion larger than these size thresholds had uptake less than or equal to normal liver, even if other lesions were PSMA-positive 2
Performance Status and Baseline Characteristics
- ECOG performance status 0-2 2
- Progressive disease documented (PSA, radiographic, or symptomatic progression) 5
Stratification Factors
Randomization was stratified by:
- Baseline lactate dehydrogenase (≤260 vs >260 IU/L)
- Presence of liver metastases
- ECOG performance status (0-1 vs 2)
- Concurrent ARPI use as part of standard of care 2, 4
Treatment Regimen
Lu-177-PSMA-617 Dosing
7.4 GBq (200 mCi) intravenously every 6 weeks 3, 1, 3, 1, 3
Number of Cycles
- Initial plan: 4 cycles
- Optional extension: up to 6 total cycles for patients with stable disease or partial response after 4 doses, per investigator discretion 2, 4
Important safety note: Analysis of cycles 5-6 showed no additional safety concerns compared to cycles 1-4, supporting the use of extended treatment in responding patients 6
Concurrent Standard of Care
Protocol-permitted standard of care included:
- ARPIs (abiraterone, enzalutamide)
- Bisphosphonates
- Denosumab
- Radiation therapy to localized targets
- Glucocorticoids 3, 1
Explicitly excluded from standard of care:
- Chemotherapy
- Immunotherapy
- Radium-223
- Investigational drugs 4
Clinical Outcomes from VISION
Efficacy Results
Overall survival: 15.3 vs 11.3 months (HR 0.62,95% CI 0.52-0.74, P<0.001) 3, 1, 3, 1, 3, 2
Radiographic progression-free survival: 8.7 vs 3.4 months (HR 0.40,99.2% CI 0.29-0.57, P<0.001) 3, 1, 3, 1, 3
Objective response rate (in measurable disease): 49% vs 1.6% 2
Safety Profile
Grade ≥3 adverse events: 52.7% vs 38% 1, 5
Most common grade ≥3 events:
Critical safety consideration: Despite higher toxicity rates, quality of life was maintained and time to symptomatic skeletal events was delayed (11.5 vs 6.8 months, HR 0.50) 7
Current Guideline Recommendations
NCCN Category 1 recommendation for patients with ≥1 PSMA-positive lesion, predominantly PSMA-positive disease, no dominant PSMA-negative lesions, who have received prior ARPI and taxane chemotherapy 3
FDA approval (March 2022) for PSMA-positive mCRPC after ARPI and taxane therapy 1, 8
Expanded FDA indication (based on PSMAfore): Also approved for patients progressing after ARPI who are appropriate candidates for delaying taxane chemotherapy 1
Imaging Agent Flexibility
While VISION used Ga-68 PSMA-11, guidelines recognize equivalency of:
All three tracers are acceptable for determining treatment eligibility 1, 9