Effectiveness of 6 Infusions of LU-177 After Two Docetaxel Infusions
Six infusions of Lutetium-177 PSMA therapy is an effective treatment option for patients who have previously received two docetaxel infusions, with evidence showing significant improvement in overall survival and progression-free survival. 1
Patient Selection and Eligibility
For patients who have received docetaxel chemotherapy, Lu-177 PSMA therapy is recommended under the following conditions:
- Confirmed metastatic castration-resistant prostate cancer (mCRPC)
- Previous treatment with at least one androgen receptor-directed therapy
- Previous treatment with taxane-based chemotherapy (such as docetaxel)
- PSMA-positive metastatic lesions confirmed by appropriate imaging
- No dominant PSMA-negative metastatic lesions 1
Efficacy of Lu-177 PSMA Therapy After Docetaxel
The National Comprehensive Cancer Network provides a category 1 recommendation for Lu-177 PSMA-617 in patients with mCRPC who have previously received taxane-based chemotherapy 1. Clinical outcomes for patients receiving Lu-177 after docetaxel include:
- Median overall survival improvement of 4 months (15.3 vs 11.3 months) compared to standard of care alone
- Median progression-free survival improvement of 5.3 months (8.7 vs 3.4 months)
- Hazard ratio of 0.62 for overall survival and 0.40 for radiographic progression-free survival 1
Administration Protocol
The recommended protocol for Lu-177 PSMA-617 consists of:
- Dosage: 7.4 GBq (200 mCi) per cycle
- Administration: Intravenous infusion over 10-30 minutes
- Frequency: Every 6 weeks
- Duration: 4-6 cycles 1
This aligns with the question regarding 6 infusions, which falls within the recommended range of treatment cycles.
Safety and Toxicity Considerations
Common adverse events associated with Lu-177 PSMA-617 include:
- Hematologic toxicities (anemia, thrombocytopenia, lymphopenia)
- Fatigue
- Dry mouth
- Nausea 1
The incidence of grade ≥3 adverse events is significantly higher with Lu-177 PSMA-617 compared to standard care alone, with hematologic toxicities being most common 1.
Emerging Evidence for Earlier Use
While the established protocol is for Lu-177 PSMA after taxane-based chemotherapy, emerging research suggests potential benefits of using Lu-177 PSMA earlier in the treatment sequence:
- A recent phase 2 study demonstrated that Lu-177 PSMA-617 was non-inferior to docetaxel in chemotherapy-naïve mCRPC patients, with a PSA response rate of 60% versus 40% for docetaxel 2
- Another phase 2 study showed that sequential Lu-177 PSMA-617 followed by docetaxel improved antitumor activity in patients with de-novo high-volume metastatic hormone-sensitive prostate cancer compared to docetaxel alone 3
Monitoring and Follow-up
For patients receiving Lu-177 PSMA therapy after docetaxel:
- Complete blood count every 2-4 weeks after treatment
- Renal and liver function tests before subsequent cycles
- Long-term follow-up with blood tests every 8-12 weeks for the first 12 months 1
Conclusion
Six infusions of Lu-177 PSMA therapy is an effective treatment option for patients who have previously received docetaxel chemotherapy, with significant improvements in overall survival and progression-free survival. The treatment is well-established for patients with mCRPC who have progressed after taxane-based chemotherapy, with a strong evidence base supporting its use in this setting.