Is Docetaxel a better initial treatment option than LU-177 (Lutetium-177) for a patient with castration-resistant prostate cancer who is in good health?

Docetaxel Should Be Used Before LU-177 in Good Health Patients with Castration-Resistant Prostate Cancer

For patients with castration-resistant prostate cancer who are in good health, docetaxel should be used before LU-177 (Lutetium-177) therapy based on established treatment sequencing guidelines and evidence-based protocols.

Treatment Algorithm for Castration-Resistant Prostate Cancer

First-Line Treatment Options

1. Docetaxel with prednisone (75 mg/m² every 3 weeks) is the standard first-line chemotherapy option for patients with castration-resistant prostate cancer who are in good health 1

   • Docetaxel has demonstrated both survival benefit and palliative benefit in symptomatic disease 1
   • The ESMO guidelines recommend docetaxel using a 3-weekly schedule for symptomatic castration-resistant disease (Level I, A evidence) 1

2. Novel hormonal agents may be considered before chemotherapy in select patients:

   • Abiraterone/prednisone
   • Enzalutamide
   • These are particularly suitable for asymptomatic or minimally symptomatic patients

Second-Line and Subsequent Treatment Options

1. LU-177-PSMA-617 is recommended after:
   • Prior treatment with at least one taxane (docetaxel)
   • Prior treatment with at least one novel androgen receptor axis inhibitor 1
   • The VISION trial showed improved overall survival (15.3 vs 11.3 months) when LU-177 was used after taxane and androgen receptor inhibitor therapy 1

Evidence Supporting This Sequence

The treatment sequence is supported by multiple high-quality guidelines:

1. AUA Guidelines: Docetaxel is considered the standard first-line therapy in metastatic castration-resistant prostate cancer 1

2. ESMO Guidelines: Docetaxel is recommended for symptomatic castration-resistant disease, while LU-177-PSMA is positioned after docetaxel and androgen receptor inhibitor therapy 1

3. NCCN Guidelines: Triplet therapies including docetaxel are recommended for high-volume metastatic disease in patients fit for chemotherapy 1

4. FDA Approval: Docetaxel is specifically indicated for metastatic castration-resistant prostate cancer in combination with prednisone 2

Treatment Response Considerations

When using docetaxel:

• Approximately 45-48% of patients will have at least a 50% decrease in PSA levels 3
• Early PSA increases (<12 weeks) after starting docetaxel should be ignored when determining progression 3
• Delay formal PSA response assessment until 12 weeks (4 cycles of 3-weekly docetaxel) 3

Potential Pitfalls and Caveats

1. Docetaxel administration schedule:

   • The standard 3-weekly regimen (75 mg/m²) with prednisone is recommended for optimal response 3, 2
   • A 2-weekly regimen (50 mg/m² on days 1 and 15 of a 4-week cycle) may be better tolerated with fewer grade 3-4 adverse events and neutropenic infections 4

2. Monitoring for toxicity:

   • Monitor for neutropenia (occurs in up to 53% with 3-weekly docetaxel) 3, 4
   • Other common side effects include fatigue, neuropathy, and fluid retention 2

3. Response assessment:

   • PSA is not always a reliable indicator of disease activity, particularly in undifferentiated or anaplastic prostate cancer 3
   • Consider PSMA-based imaging rather than relying solely on PSA measurements 3

4. Docetaxel rechallenge:

   • Patients who responded well to first-line docetaxel (≥50% PSA reduction) may benefit from docetaxel rechallenge if disease progression occurs after a treatment-free interval 5, 6

Emerging Evidence

A small randomized phase 2 trial (n=40) comparing LU-177-PSMA-617 to docetaxel in chemotherapy-naïve mCRPC patients showed that LU-177-PSMA-617 was non-inferior to docetaxel with better quality-of-life outcomes and fewer grade ≥3 adverse events 7. However, this is a single small study and does not override the established treatment guidelines that recommend docetaxel before LU-177 therapy.

In conclusion, while treatment decisions should consider individual patient factors, the established treatment pathway for patients with castration-resistant prostate cancer in good health supports using docetaxel before LU-177 therapy based on current high-quality guidelines and evidence.