Efficacy of Lutetium-177 (LU-177) for Patients with High PSMA Expression and No Other Tumors on FBG Scan
Lutetium-177 PSMA therapy significantly improves overall survival and progression-free survival in patients with high PSMA expression and no PSMA-negative lesions, with a median overall survival of 15.3 months versus 11.3 months for standard of care alone. 1
Evidence for Efficacy
The efficacy of Lu-177 PSMA therapy is well-established based on high-quality evidence from the phase III VISION trial:
Overall Survival Benefit: Lu-177 PSMA-617 plus standard of care improved median overall survival to 15.3 months compared to 11.3 months with standard of care alone (HR 0.62; 95% CI, 0.52-0.74; p<0.001) 1, 2
Progression-Free Survival: Median progression-free survival was significantly extended to 8.7 months versus 3.4 months (HR 0.40; 99.2% CI, 0.29-0.57; p<0.001) 1
Patient Selection: The VISION trial specifically enrolled patients with:
- PSMA-positive metastatic lesions
- No PSMA-negative lesions on Ga-68 PSMA-11 PET/CT imaging
- Previous treatment with androgen receptor-directed therapy and taxane-based chemotherapy 1
Treatment Protocol and Recommendations
The American Urological Association and NCCN provide strong recommendations for Lu-177 PSMA therapy:
Standard Regimen: 7.4 GBq (200 mCi) every 6 weeks for 4-6 cycles 1, 2
Patient Selection Criteria:
Strength of Recommendation: The NCCN Prostate Cancer Panel gives Lu-177-PSMA-617 a category 1 recommendation for appropriately selected patients 1
Safety Profile and Adverse Events
Lu-177 PSMA therapy has a manageable safety profile, though certain adverse events require monitoring:
Common Adverse Events: Grade ≥3 adverse events occurred in 52.7% of patients receiving Lu-177-PSMA-617 versus 38% with standard of care alone 1
Specific Toxicities: The most common grade 3-4 adverse events include:
- Anemia
- Thrombocytopenia
- Lymphopenia
- Fatigue 1
Quality of Life: Despite higher rates of adverse events, quality of life was maintained in the VISION trial 1
Important Considerations and Caveats
When considering Lu-177 PSMA therapy, several important factors should be considered:
PSMA PET Imaging: Confirmation of PSMA expression is mandatory before treatment. PSMA-negative lesions are defined as metastatic disease that lacks PSMA uptake, including:
- Bone with soft tissue components ≥1.0 cm
- Lymph nodes ≥2.5 cm in short axis
- Solid organ metastases ≥1.0 cm in size 1
Imaging Options: While the FDA approved Ga-68 PSMA-11 for use with Lu-177-PSMA-617, F-18 piflufolastat PSMA and F-18 flotufolastat PSMA can also be used due to their equivalency 1
Renal Function: Patients with mild to moderate renal impairment may be at greater risk of toxicity and require frequent monitoring of renal function and adverse reactions 3
Treatment Sequence: Lu-177 PSMA therapy is currently approved for use after failure of both androgen receptor pathway inhibition and taxane-based chemotherapy 1
Emerging Evidence
While the current approval is for mCRPC after standard therapies, emerging research suggests potential benefits in earlier disease states:
Early data shows promising efficacy and safety of Lu-177 PSMA-617 in patients with high-volume metastatic hormone-sensitive prostate cancer, with 50% of patients achieving undetectable PSA and 90% showing ≥50% PSA decline 4
Higher baseline PSMA expression levels in bone metastases may predict better treatment response, with SUVmax >10.50 associated with improved outcomes 5
In conclusion, Lu-177 PSMA therapy represents a highly effective treatment option for patients with high PSMA expression and no PSMA-negative lesions, offering significant improvements in survival outcomes with a manageable safety profile when used according to established guidelines.