What is the recommended use of Pluvicto (lutetium-177 vipivotide tetraxetan) in patients with prostate cancer?

Recommended Use of Pluvicto (Lutetium-177 Vipivotide Tetraxetan) in Prostate Cancer

Pluvicto is indicated for adult patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. 1

Patient Selection Criteria

• Patients must have confirmed metastatic castration-resistant prostate cancer (mCRPC) 1
• Patients must have received prior treatment with:
  • Androgen receptor (AR) pathway inhibition 1, 2
  • Taxane-based chemotherapy 1, 2
• PSMA-positivity must be confirmed using LOCAMETZ or another approved PSMA-11 imaging agent 1
• Patients should have PSMA-expressing tumors without PSMA non-expressing lesions on PET-PSMA imaging 3, 4

Treatment Protocol

• The recommended dosage is 7.4 GBq (200 mCi) administered intravenously every 6 weeks 1, 2
• Treatment continues for up to 6 doses, or until disease progression or unacceptable toxicity 1, 2
• Dosage modifications are required for certain adverse reactions:
  • For Grade 2 myelosuppression: Withhold until improvement to Grade 1 or baseline 1
  • For Grade ≥3 myelosuppression: Withhold until improvement and reduce dose to 5.9 GBq (160 mCi) 1
  • If treatment delay persists >4 weeks, discontinue Pluvicto 1

Clinical Evidence Supporting Use

• The VISION trial demonstrated that Pluvicto plus 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) 3, 2
  • Radiographic progression-free survival (8.7 vs 3.4 months; HR 0.40,99.2% CI 0.29-0.57, P<0.001) 3
• The TheraP trial showed higher PSA response rates with Lu-177-PSMA-617 (66%) compared to cabazitaxel (37%) in patients previously treated with docetaxel 4
• Lu-177-PSMA therapy has fewer grade 3-4 adverse events (33%) compared to alternative treatments like cabazitaxel (53%) 4

Monitoring and Safety Considerations

• Blood counts, renal, and hepatic function should be checked before each treatment cycle 3
• Radioprotection precautions must be followed according to national and local regulations 3
• Common adverse reactions (≥20%) include:
  • Fatigue, dry mouth, nausea, anemia, decreased appetite, and constipation 2
• Common laboratory abnormalities (≥30%) include:
  • Decreased lymphocytes, hemoglobin, leukocytes, platelets, calcium, and sodium 2
• Multidisciplinary collaboration is recommended for optimal utilization of Pluvicto 3

Position in Treatment Algorithm for mCRPC

• Pluvicto is recommended after patients have progressed on:
  • A novel androgen receptor axis inhibitor (abiraterone, enzalutamide, apalutamide, or darolutamide) 3, 1
  • Docetaxel chemotherapy 3, 1
• ESMO guidelines specifically recommend 177Lu-PSMA-617 for patients with mCRPC who have received a novel androgen receptor axis inhibitor and docetaxel, with an ESMO-MCBS v1.1 score of 4 3
• Pluvicto should be considered alongside cabazitaxel as treatment options after progression on initial therapies 3

Clinical Pearls and Pitfalls

• Patient selection is critical - ensure proper PSMA imaging is performed before initiating treatment 1
• Continuing Lu-177 therapy beyond two cycles is reasonable for patients who have not progressed, even if lesions have not yet shown significant reduction 4
• Myelosuppression can be cumulative with additional cycles, requiring careful monitoring 4
• Pluvicto was FDA-approved on March 23,2022, as the first targeted radioligand therapy for eligible men with PSMA-positive mCRPC 5, 6