What is the effectiveness of Lutetium-177 (LU-177) after two infusions of Docetaxel?

Effectiveness of Lutetium-177 After Two Docetaxel Infusions

Lutetium-177 (Lu-177) PSMA therapy is highly effective after two docetaxel infusions, demonstrating significant improvement in overall survival (15.3 vs 11.3 months) and progression-free survival (8.7 vs 3.4 months) compared to standard of care alone in patients with metastatic castration-resistant prostate cancer (mCRPC). 1

Evidence for Lu-177 Effectiveness After Docetaxel

Lu-177 PSMA-617 (vipivotide tetraxetan) has strong evidence supporting its use in patients who have previously received taxane-based chemotherapy:

• The VISION trial demonstrated that Lu-177 PSMA-617 combined with best standard of care significantly improved:

  • Overall survival: 15.3 vs 11.3 months (HR 0.62,95% CI 0.52-0.74, P < 0.001)
  • Radiographic progression-free survival: 8.7 vs 3.4 months (HR 0.40,99.2% CI 0.29-0.57, P < 0.001) 1

• The NCCN Prostate Cancer Panel gives Lu-177 PSMA-617 a category 1 recommendation for patients with:

  • At least one PSMA-positive lesion
  • Previous treatment with androgen receptor-directed therapy and taxane-based chemotherapy
  • No dominant PSMA-negative metastatic lesions 1

Patient Selection Criteria

For optimal effectiveness after docetaxel therapy, patients should meet these criteria:

• PSMA-positive metastatic lesions confirmed by appropriate imaging (Ga-68 PSMA-11, F-18 piflufolastat PSMA, or F-18 flotufolastat PSMA) 1
• No dominant PSMA-negative metastatic lesions (defined as):
  • 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
• Previous treatment with:
  • At least one androgen receptor-directed therapy
  • At least one taxane-based chemotherapy regimen 1

Administration Protocol

The recommended Lu-177 PSMA-617 administration protocol is:

• Dosage: 7.4 GBq (200 mCi) per cycle
• Frequency: Every 6 weeks
• Duration: 4-6 cycles
• Administration method: Intravenous infusion over 10-30 minutes 2

Expected Outcomes and Toxicity Profile

Patients receiving Lu-177 after docetaxel can expect:

Benefits:

• Median overall survival improvement of 4 months (15.3 vs 11.3 months)
• Median progression-free survival improvement of 5.3 months (8.7 vs 3.4 months) 1

Common adverse events:

• Hematologic toxicities (particularly anemia, thrombocytopenia, lymphopenia)
• Fatigue
• Dry mouth
• Nausea 1, 2

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.

Comparison with Other Therapies

When comparing Lu-177 to other therapies after docetaxel:

• Lu-177 PSMA-617 shows similar efficacy patterns to radium-223 but with different targeting mechanisms:

  • Radium-223 targets bone metastases specifically
  • Lu-177 PSMA-617 targets PSMA-expressing cells regardless of location 1

• Recent evidence suggests Lu-177 may be effective even earlier in the treatment course:

  • The UpFrontPSMA trial showed improved antitumor activity when Lu-177 was used before docetaxel in hormone-sensitive disease 3
  • A phase 2 randomized trial demonstrated that Lu-177 was noninferior to docetaxel in chemotherapy-naïve mCRPC patients 4

Clinical Considerations and Caveats

Important considerations when using Lu-177 after docetaxel:

• Patient monitoring should include:

  • 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 2

• Re-challenge with Lu-177 is possible after disease progression following initial treatment:

  • Minimum interval of 6 months after completion of initial treatment
  • Typically consists of 1-2 additional cycles 2
  • Some evidence suggests combining low-dose docetaxel as a radiosensitizer with re-challenge Lu-177 may be effective 5

• Radiation safety protocols must be followed according to local regulations, with patients observing rigorous hygiene for 1 week following treatment 2

Lu-177 PSMA therapy represents a significant advancement in the treatment of mCRPC after docetaxel failure, offering meaningful survival benefits with a manageable toxicity profile.