What therapy should be tried for Prostate-Specific Membrane Antigen (PSMA) positive prostate cancer if Docetaxel does not work?

Treatment Options for PSMA-Positive Prostate Cancer After Docetaxel Failure

For PSMA-positive prostate cancer that has progressed after docetaxel treatment, Lutetium-177 PSMA-617 (177Lu-PSMA-617) therapy is strongly recommended as the most effective next-line treatment option. 1

Evidence-Based Treatment Algorithm

First-Line Option After Docetaxel Failure:

• 177Lu-PSMA-617 therapy
  • Requires confirmation of PSMA expression via PSMA PET imaging 1
  • Standard regimen: 7.4 GBq (200 mCi) every 6 weeks for 4-6 cycles 2
  • Strong evidence of survival benefit (Level A evidence) 1

Key Clinical Trial Evidence:

• The VISION trial demonstrated that 177Lu-PSMA-617 plus standard of care significantly improved:
  • Overall survival: 15.3 vs 11.3 months (HR 0.62, p<0.001) 1, 2
  • Progression-free survival: 8.7 vs 3.4 months (HR 0.40, p<0.001) 1, 2

Patient Selection Criteria:

1. Confirmed mCRPC with PSMA-positive disease on PET imaging
2. Previous treatment with docetaxel and androgen receptor pathway inhibitor
3. No dominant PSMA-negative metastatic lesions 1, 2

Alternative Options (if 177Lu-PSMA-617 is not available/suitable):

• Cabazitaxel (second-line taxane) 1
  • Particularly effective after docetaxel failure
  • ESMO-MCBS score: 3 1

Clinical Considerations

Monitoring During Treatment:

• Regular imaging is essential even without PSA progression
• Perform imaging at least annually for mCRPC patients without PSA progression 1
• Monitor for treatment-related adverse events, particularly:
  • Grade 1-2: dry mouth (87%), nausea (50%), fatigue (50%)
  • Grade 3-4: thrombocytopenia (13%) 3

Emerging Approaches:

• Re-challenge with 177Lu-PSMA-617 in initial responders shows promise 4
• Combination of low-dose docetaxel with 177Lu-PSMA-617 as a radiosensitizer may enhance efficacy 4
• Earlier use of 177Lu-PSMA-617 in the disease course is being investigated 5, 6

Important Caveats

• PSMA PET imaging is mandatory before considering 177Lu-PSMA-617 therapy to confirm PSMA expression 1
• Cross-resistance between androgen receptor pathway inhibitors (abiraterone and enzalutamide) means switching between these agents may not be optimal after docetaxel failure 1
• The TheraP trial showed superior PSA response with 177Lu-PSMA-617 compared to cabazitaxel (66% vs 37%) with fewer grade 3-4 adverse events (33% vs 53%) 1
• Biomarker-based patient selection for 177Lu-PSMA-617 therapy remains an area of active research 7

177Lu-PSMA-617 therapy represents a significant advancement in the treatment of PSMA-positive prostate cancer after docetaxel failure, offering improved survival outcomes with manageable toxicity compared to standard of care.