When to consider Lutetium-177 (Lu-177) for metastatic castration-resistant prostate cancer (mCRPC) after limited Docetaxel (generic name: Docetaxel) treatment?

Using Lutetium-177 (Lu-177) After Limited Docetaxel Treatment in mCRPC

Lu-177-PSMA therapy is strongly recommended for patients with metastatic castration-resistant prostate cancer (mCRPC) who have received limited docetaxel treatment (such as only two infusions), especially if they have PSMA-positive disease confirmed by imaging. 1

Evidence Supporting Lu-177 After Limited Docetaxel

• The NCCN guidelines specifically highlight the TheraP trial, which demonstrated that Lu-177-PSMA-617 achieved a significantly higher PSA response rate (66%) compared to cabazitaxel (37%) in patients who had previously received docetaxel, regardless of the number of cycles 1
• Lu-177-PSMA therapy has shown efficacy in patients who have progressed after taxane-based chemotherapy, with fewer grade 3-4 adverse events (33%) compared to alternative treatments like cabazitaxel (53%) 1
• Standard Lu-177-PSMA therapy typically consists of 3-5 cycles administered at 6-12 week intervals, with each cycle delivering 5.55-7.4 GBq of radioactivity to PSMA-expressing tumor cells 2

Patient Selection Criteria

• Patients should have:
  • Confirmed metastatic castration-resistant prostate cancer 1
  • Previous treatment with at least one androgen receptor pathway inhibitor 3
  • Limited response or progression after docetaxel treatment 1
  • PSMA-positive disease confirmed by appropriate imaging (such as 68Ga-PSMA-11 PET/CT) 4

Clinical Evidence for Efficacy

• The VISION trial demonstrated that Lu-177-PSMA-617 significantly prolonged both imaging-based progression-free survival (median 8.7 vs 3.4 months) and overall survival (median 15.3 vs 11.3 months) compared to standard care in patients who had received at least one taxane regimen 4
• A phase 2 non-inferiority trial comparing Lu-177-PSMA-617 to docetaxel in chemotherapy-naïve mCRPC patients showed that Lu-177-PSMA-617 was non-inferior to docetaxel with a PSA response rate of 60% vs 40% 5
• Quality of life outcomes improved significantly with Lu-177-PSMA-617 compared to docetaxel 5

Safety Profile and Side Effects

• The most common adverse events with Lu-177 therapy include:
  • Hematologic toxicities: anemia, thrombocytopenia, and lymphopenia 3
  • Fatigue 3
  • Nausea and vomiting (often related to amino acid co-infusion) 3
• Treatment-emergent grade ≥3 adverse events occur less frequently with Lu-177-PSMA-617 (30%) than with docetaxel (50%) 5

Important Considerations

• Regular monitoring of hematologic parameters is essential as myelosuppression can be cumulative with additional cycles 2
• Continuing Lu-177 therapy beyond two cycles is reasonable and recommended for patients who have not progressed, even if lesions have not yet shown significant reduction 2
• The European Association of Nuclear Medicine recommends 4-6 cycles of Lu-177-PSMA treatment at 6-week intervals for mCRPC 2

Treatment Algorithm

1. Confirm mCRPC diagnosis and progression after limited docetaxel treatment 1
2. Verify PSMA expression with appropriate imaging 4
3. Assess patient's performance status and organ function 1
4. If suitable, initiate Lu-177-PSMA therapy with standard dosing of 6.0-7.4 GBq per cycle every 6-8 weeks 5, 4
5. Monitor response after each cycle with PSA measurements and imaging as appropriate 1
6. Continue treatment for 4-6 cycles if clinical benefit is observed and toxicity is manageable 2

Lu-177-PSMA therapy represents an effective treatment option with favorable safety profile for patients with mCRPC who have received limited docetaxel treatment, offering improved survival outcomes and quality of life compared to continuing with conventional chemotherapy.