Lutetium-177 (Lu-177) PSMA-617 After Docetaxel Provides Survival Benefit in PSMA-Positive Metastatic Prostate Cancer
Lu-177 PSMA-617 therapy is recommended for patients with metastatic castration-resistant prostate cancer (mCRPC) who have PSMA-positive disease and have previously received docetaxel, as it significantly improves overall survival compared to standard of care alone. 1
Evidence for Sequential Therapy
The strongest evidence for this treatment sequence comes from the phase III VISION trial, which demonstrated:
- Median overall survival improved to 15.3 months with Lu-177 PSMA-617 plus standard of care versus 11.3 months with standard of care alone (HR, 0.62; 95% CI, 0.52–0.74; P<.001) 1
- Median progression-free survival improved to 8.7 months with Lu-177 PSMA-617 plus standard of care versus 3.4 months with standard of care alone (HR, 0.40; 99.2% CI, 0.29–0.57; P<.001) 1
Patient Selection Criteria
Lu-177 PSMA-617 should be used in patients who meet all these criteria:
- Confirmed mCRPC with PSMA-positive lesions on gallium-68 PSMA-11 PET/CT imaging
- No dominant PSMA-negative metastatic lesions
- Previous treatment with:
- Androgen receptor-directed therapy
- Taxane-based chemotherapy (docetaxel)
Treatment Protocol
- Standard Lu-177 PSMA-617 regimen: 7.4 GBq (200 mCi) every 6 weeks for 4-6 cycles 1
- Safety data support administering up to 6 cycles with no additional safety concerns compared to 4 cycles 2
Adverse Effects Management
Common adverse events include:
- Hematologic: Anemia, thrombocytopenia, lymphopenia
- Non-hematologic: Fatigue, xerostomia, nausea
Long-term Safety Considerations
- Monitor for therapy-related myeloid neoplasms (t-MN), which have been reported in approximately 1.3% of patients receiving Lu-177 PSMA therapy 3
- Regular complete blood counts should be performed during and after treatment
Emerging Evidence
Recent research suggests potential benefits of Lu-177 PSMA-617 in earlier disease settings:
- The UpFrontPSMA trial showed that Lu-177 PSMA-617 followed by docetaxel improved antitumor activity in hormone-sensitive prostate cancer compared to docetaxel alone 4
- A phase 2 randomized trial demonstrated that Lu-177 PSMA-617 had comparable overall survival to docetaxel in chemotherapy-naïve mCRPC patients (median OS 19.0 vs 15.0 months, respectively) 5
Treatment Algorithm
- Confirm PSMA expression with Ga-68 PSMA-11 PET/CT imaging
- Verify absence of dominant PSMA-negative lesions
- Ensure patient has received prior docetaxel and androgen receptor-directed therapy
- Administer Lu-177 PSMA-617 at 7.4 GBq every 6 weeks
- Continue for 4-6 cycles if well-tolerated and clinically beneficial
- Monitor for hematologic toxicities during and after treatment
The NCCN Prostate Cancer Panel gives a category 1 recommendation for Lu-177 PSMA-617 in this setting, indicating high-level evidence and uniform consensus that this intervention is appropriate 1.