What treatment options are available for patients with late-stage metastasis, specifically Lutetium-177 (Lutetium) PSMA (Prostate-Specific Membrane Antigen) therapy?

Lutetium-177 PSMA Therapy for Late-Stage Metastatic Prostate Cancer

Lutetium-177 PSMA-617 therapy is strongly recommended for patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously received docetaxel and androgen pathway inhibitor treatment and have PSMA-positive disease confirmed by imaging. 1

Patient Selection Criteria

• Lutetium-177 PSMA-617 therapy is indicated for patients with:

  • Progressive mCRPC after prior treatment with at least one androgen receptor pathway inhibitor and taxane-based chemotherapy 1, 2
  • Positive PSMA PET imaging confirming PSMA expression in tumor lesions 2
  • No PSMA-negative metastatic lesions that could escape targeting 3

• Particularly beneficial for patients with:

  • Bone-predominant metastatic disease 1
  • Limited response to previous standard therapies 1, 2

Clinical Evidence Supporting Lutetium-177 PSMA Therapy

• The VISION trial demonstrated that Lutetium-177 PSMA-617 plus 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) 2, 1
  • Imaging-based progression-free survival (8.7 vs. 3.4 months; HR 0.40; 99.2% CI: 0.29-0.57; P<0.001) 2

• The TheraP trial showed superior PSA response rates with Lutetium-177 PSMA-617 (66%) compared to cabazitaxel (37%) in patients previously treated with docetaxel 1

• Real-world data from the REALITY Study showed:

  • ≥50% PSA reduction in 52% of heavily pretreated patients 4
  • Median PSA progression-free survival of 5.5 months 4
  • Median overall survival of 14.5 months 4

Treatment Protocol

• Standard treatment consists of:

  • 4-6 cycles of Lutetium-177 PSMA-617 at 6-week intervals 3, 2
  • Typical dose of 7.4 GBq (200 mCi) per cycle 2
  • Administered intravenously 2

• Pre-treatment assessment should include:

  • PSMA PET imaging to confirm PSMA expression 2
  • Complete blood count, renal and hepatic function tests 3
  • Performance status evaluation 3

Safety Profile

• Most common adverse events include:

  • Grade 1-2 dry mouth (reported in up to 87% of patients) 5
  • Fatigue (50% of patients) 5
  • Nausea (50% of patients) 5

• More serious but less common adverse events:

  • Grade 3-4 thrombocytopenia (4.3-13% of patients) 5, 4
  • Grade 3-4 anemia (7.1-30% of patients) 4, 6
  • Grade 3-4 lymphopenia (2.8% of patients) 4

• The incidence of grade 3 or higher adverse events is higher with Lutetium-177 PSMA-617 than with standard care alone (52.7% vs. 38.0%), but quality of life is not adversely affected 2

Emerging Applications

• Potential use in earlier disease stages:

  • A pilot study in low-volume hormone-sensitive metastatic prostate cancer showed promising results with no grade 3-4 adverse events 7
  • 50% of patients showed PSA response of more than 50% 7
  • One patient achieved complete response on PSMA-PET imaging 7

• Combination approaches:

  • Caution advised when combining with abiraterone acetate based on the ERA-223 trial results 1
  • Bone-targeted agents should be started before Lutetium-177 PSMA therapy to reduce fracture risk 1

Monitoring and Follow-up

• Regular monitoring during treatment:

  • PSA levels before each cycle 3
  • Complete blood count, renal and hepatic function 3
  • Clinical assessment for symptoms and adverse events 3

• Response assessment:

  • PSA response (≥50% decline from baseline) 5
  • Imaging response using conventional and PSMA PET imaging 5
  • Pain and quality of life assessments 5

Lutetium-177 PSMA therapy represents a significant advancement in the treatment of late-stage metastatic prostate cancer, offering improved survival and quality of life for patients who have progressed on standard therapies.