Recalling LU-177 vs. Extended Continuous Treatment for Prostate Cancer
Recalling (rechallenge) of LU-177 PSMA therapy shows better efficacy than continuous extended treatment for prostate cancer patients, with significantly higher PSA response rates (90.4% vs 61.9%) and longer overall survival (40.2 vs 23.2 months). 1
Treatment Approaches with LU-177 PSMA Therapy
Standard Treatment Protocol
- Standard LU-177 PSMA therapy consists of 7.4 GBq (200 mCi) administered intravenously every 6 weeks for 4-6 cycles 2
- The VISION trial demonstrated significant benefits with LU-177 PSMA-617 plus standard of care compared to standard of care alone:
- Improved median overall survival: 15.3 vs 11.3 months (HR 0.62, p<0.001)
- Improved median progression-free survival: 8.7 vs 3.4 months (HR 0.40, p<0.001) 2
Extended Treatment Options
Option 1: Continuous Extended Treatment
- Involves uninterrupted continuation of therapy beyond 6 cycles
- Median overall survival from initiation: 23.2 months
- Initial PSA response rate (≥50% decline): 61.9% 1
Option 2: Rechallenge Treatment (Preferred)
- Involves reexposure to LU-177 PSMA therapy after a treatment break
- Median overall survival from initiation: 40.2 months (significantly longer than continuous treatment)
- Initial PSA response rate (≥50% decline): 90.4% (significantly higher than continuous treatment, p=0.006)
- PSA decline ≥50% observed in 37.1% of patients after first rechallenge 1
Safety Considerations
Extended therapy with LU-177 PSMA (both continuous and rechallenge) shows comparable safety profiles:
- Grade 3-4 anemia: 16.3% (continuous) vs 19.1% (rechallenge), p=0.6
- Grade 3-4 leukocytopenia: 2.3% (continuous) vs 3.0% (rechallenge), p=0.3
- Grade 3-4 thrombocytopenia: 7.0% (continuous) vs 4.4% (rechallenge), p=0.3
- Grade 3-4 renal toxicity: 4.7% (continuous) vs 7.4% (rechallenge), p=0.2 1
The VISION trial safety analysis showed that longer exposure to LU-177 PSMA-617 was not associated with higher toxicity risk, supporting the use of up to 6 cycles in patients benefiting from and tolerating this therapy 3
Monitoring Response and Treatment Decisions
- PSA monitoring should be performed by cycle, with formal response evaluation no earlier than 12 weeks after treatment initiation 2
- PSMA PET imaging is recommended at baseline, after every 2 cycles (approximately every 12-16 weeks), and at least annually thereafter 2
- Post-therapy imaging should be performed after each Lu-177 infusion (typically 1-24 hours post-infusion) using SPECT/CT 2
Clinical Implications
The rechallenge approach allows for treatment breaks which may:
- Reduce cumulative toxicity
- Preserve bone marrow function
- Potentially resensitize cancer cells to the treatment
- Improve quality of life during treatment breaks
Patients who initially respond well to LU-177 PSMA therapy are particularly good candidates for the rechallenge approach when they show disease progression after the initial treatment course
Pitfalls and Caveats
- Not all patients will respond to rechallenge therapy (37.1% PSA response rate with rechallenge)
- Patient selection is crucial - candidates should have:
- Confirmed metastatic castration-resistant prostate cancer
- High PSMA expression on PET imaging
- No dominant PSMA-negative metastatic lesions 2
- Regular monitoring of hematological parameters and renal function is essential before each cycle to assess for toxicity 2
- PSA patterns can vary, including initial rise followed by decline, plateau, or delayed response, which should be considered when evaluating treatment efficacy 2
Based on the most recent evidence, the rechallenge approach with LU-177 PSMA therapy demonstrates superior outcomes compared to continuous extended treatment for prostate cancer patients who have previously responded to this therapy.