When is it recommended to continue Lutetium-177 (Lu-177) infusions for prostate cancer beyond six infusions?

Continuing Lu-177 Infusions Beyond Six Cycles for Prostate Cancer

Lu-177 therapy should be continued beyond six cycles in patients with metastatic castration-resistant prostate cancer who show ongoing clinical benefit without significant toxicity, as extended therapy has demonstrated safety and efficacy with favorable survival outcomes of 31.3 months from first administration. 1

Standard Treatment Protocol for Lu-177 in Prostate Cancer

• The FDA-approved regimen for Lu-177-PSMA-617 (Pluvicto) is 7.4 GBq (200 mCi) intravenously every 6 weeks for up to 6 doses, or until disease progression or unacceptable toxicity 2, 3
• Lu-177-PSMA-617 is indicated for PSMA-positive metastatic castration-resistant prostate cancer in patients previously treated with androgen receptor pathway inhibition and taxane-based chemotherapy 2
• The VISION trial that led to FDA approval used a protocol of 4-6 cycles of Lu-177-PSMA-617 at 6-week intervals, demonstrating improved overall survival (15.3 vs 11.3 months) compared to standard of care alone 4

Evidence Supporting Continuation Beyond Six Cycles

• A 2024 German multicenter study demonstrated that extended Lu-177-PSMA therapy beyond 6 cycles is safe and not associated with increased grade 3-4 toxicity 1
• Patients receiving extended treatment experienced favorable median survival of 31.3 months from first administration, significantly longer than the 15.3 months observed in the standard 6-cycle protocol from the VISION trial 1
• Extended therapy can be administered either as continuous treatment without interruption or as rechallenge treatment after a therapy break, with median cumulative doses of 57.4 GBq and 60.8 GBq respectively 1

Criteria for Continuing Beyond Six Cycles

• Continuation should be considered for patients who:
  • Show ongoing clinical benefit from initial treatment cycles 1
  • Have preserved PSMA expression on follow-up imaging 4
  • Maintain adequate organ function, particularly renal function and bone marrow reserve 2
  • Have not reached cumulative dose limits that would increase risk of toxicity 1

Safety Considerations for Extended Treatment

• Extended Lu-177 therapy has not been associated with increased grade 3-4 toxicity compared to standard treatment 1
• Toxicity rates remain comparable between continuous treatment and rechallenge approaches:
  • Anemia (grade 3-4): 16.3% in continuous vs. 19.1% in rechallenge treatment 1
  • Leukocytopenia (grade 3-4): 2.3% in continuous vs. 3.0% in rechallenge treatment 1
  • Thrombocytopenia (grade 3-4): 7.0% in continuous vs. 4.4% in rechallenge treatment 1
  • Renal toxicity (grade 3-4): 4.7% in continuous vs. 7.4% in rechallenge treatment 1

Monitoring During Extended Treatment

• Complete blood count should be performed regularly between cycles to monitor for myelosuppression 2
• Renal function tests should be evaluated before each subsequent cycle 2
• If blood values fall below acceptable limits, options include:
  • Reducing the administered activity by 20% to 5.9 GBq (160 mCi) 2
  • Extending the interval between cycles up to 10 weeks 2
  • Interrupting therapy if toxicity persists 2

Treatment Response Assessment

• Response evaluation should include:
  • PSA levels (a 50% PSA decline was observed in 37.1% of patients after first rechallenge) 1
  • PSMA PET/CT imaging to assess tumor response and confirm persistent PSMA expression 1
  • Clinical assessment of symptoms and quality of life 5

Practical Approach to Extended Treatment

• For patients who complete 6 cycles with good response but eventual progression:
  • Consider rechallenge with Lu-177-PSMA after a treatment break 1
  • Verify persistent PSMA expression with imaging before rechallenge 4
• For patients with ongoing response after 6 cycles without significant toxicity:
  • Consider continuous treatment without interruption 1
  • Monitor closely for cumulative toxicity 2

Common Pitfalls and Caveats

• Patients must maintain adequate bone marrow function for extended treatment, as cumulative myelosuppression can occur 2
• Renal function must be preserved, as the kidneys are a critical organ at risk during Lu-177 therapy 2
• Treatment should be discontinued if a treatment delay due to adverse reactions persists for more than 4 weeks 2
• If dose reduction is required and further adverse reactions occur that would necessitate additional dose reduction, treatment must be discontinued 2