Should a patient with metastatic prostate cancer switch from Docetaxel (chemotherapy agent) to Lu-177 (Lutetium-177) infusions if Docetaxel is effective?

Management of Metastatic Prostate Cancer: Docetaxel vs. Lu-177 PSMA

If Docetaxel is effectively reducing metastatic prostate cancer, you should not switch to Lu-177 infusions but rather continue with the effective Docetaxel therapy until disease progression occurs. 1

Treatment Sequencing in Metastatic Castration-Resistant Prostate Cancer (mCRPC)

When to Continue Docetaxel

• Docetaxel remains the preferred first-line chemotherapy treatment for mCRPC when it is showing effectiveness with acceptable toxicity 1
• Patients should continue receiving docetaxel for up to 10 cycles if there is no disease progression and no prohibitive toxicities 1
• Effective treatment should not be changed when clinical benefit is being achieved, as this follows the principle of continuing therapy until progression 1

When to Consider Lu-177 PSMA Therapy

• Lu-177 PSMA-617 should only be offered to patients with progressive mCRPC who have previously received docetaxel and an androgen pathway inhibitor with a positive PSMA PET imaging study 1
• The 2023 AUA/SUO guidelines provide a strong recommendation (Evidence Level: Grade B) for Lu-177 PSMA-617 only after disease progression on docetaxel 1
• NCCN guidelines recommend Lu-177 PSMA-617 as a category 1 option only for patients who have been previously treated with androgen receptor-directed therapy and taxane-based chemotherapy 1

Evidence Supporting Treatment Sequencing

Lu-177 PSMA After Docetaxel Failure

• The phase 3 VISION study demonstrated that Lu-177 PSMA-617 improved both progression-free survival (8.7 vs 3.4 months) and overall survival (15.3 vs 11.3 months) compared to standard of care alone in patients who had previously failed docetaxel 1
• Before considering Lu-177 PSMA-617, patients must undergo PSMA PET imaging to confirm PSMA-positive disease 1
• Lu-177 PSMA-617 is specifically indicated for PSMA-positive M1 CRPC that has progressed after androgen receptor pathway inhibition and taxane-based chemotherapy 1

Monitoring During Docetaxel Treatment

• For patients on docetaxel without PSA progression or new symptoms, imaging should be performed at least annually to monitor for radiographic progression 1
• Approximately 24.5% of mCRPC patients may have radiographic progression without PSA progression, highlighting the importance of routine imaging 1

Practical Considerations

Docetaxel Dosing and Management

• Standard docetaxel dosing for mCRPC is 75 mg/m² every 3 weeks with prednisone 2
• Dose reductions to 60 mg/m² should be considered for patients who experience febrile neutropenia, severe cutaneous reactions, or moderate neurosensory symptoms 2
• If toxicities persist at the reduced dose, treatment should be discontinued 2

Lu-177 PSMA Requirements

• Patients must have at least one PSMA-positive metastatic lesion and no dominant PSMA-negative metastatic lesions on Ga-68 PSMA-11 PET/CT imaging 1
• PSMA-negative lesions are defined as metastatic disease that lacks PSMA uptake including bone with soft tissue components ≥1.0 cm, lymph nodes ≥2.5 cm in short axis, and solid organ metastases ≥1.0 cm in size 1

Emerging Evidence and Future Directions

• Recent research suggests Lu-177 PSMA may have potential benefit in hormone-sensitive prostate cancer, but this is still investigational and not standard of care 3
• The TheraP trial showed higher PSA response rates with Lu-177 PSMA-617 compared to cabazitaxel in patients previously treated with docetaxel (66% vs 37%) 1
• Combination approaches using Lu-177 PSMA with low-dose docetaxel as a radiosensitizer are being investigated but remain experimental 4

Common Pitfalls to Avoid

• Switching from an effective therapy prematurely can compromise disease control and patient outcomes 1
• Not performing regular imaging during treatment may miss radiographic progression in patients without PSA progression 1
• Using Lu-177 PSMA-617 before docetaxel failure is not supported by current guidelines and may limit future treatment options 1