¹⁷⁷Lu-PSMA-617 Consolidation Therapy After Docetaxel in Patients with Synchronous High-Volume Metastatic...

Area of Science:

• Nuclear Medicine
• Oncology
• Radiopharmaceutical Therapy

Background:

• Metastatic castration-resistant prostate cancer (mCRPC) treatment with 177Lu-PSMA-617 has shown survival benefits.
• Limited data exist regarding 177Lu-PSMA-617 efficacy in the hormone-sensitive prostate cancer setting.
• Consolidation therapy with 177Lu-PSMA-617 is being investigated for residual disease post-chemohormonal treatment in mHSPC.

Purpose of the Study:

• To evaluate 177Lu-PSMA-617 as consolidation therapy for synchronous high-volume metastatic hormone-sensitive prostate cancer (mHSPC) with residual disease after docetaxel.
• To assess the proportion of patients achieving prostate-specific antigen (PSA) levels ≤ 0.2 ng/mL at 6 months post-randomization.
• To determine secondary endpoints including radiographic response, progression-free survival (PFS), and toxicity.

Main Methods:

• An investigator-initiated, randomized, parallel-group, open-label phase 2 trial (CONSOLIDATE).
• Patients with synchronous high-volume mHSPC and residual nonprogressive disease after docetaxel were randomized (1:1) to 177Lu-PSMA-617 plus standard of care or standard of care alone.
• Primary endpoint: proportion of patients with PSA ≤ 0.2 ng/mL at 6 months. Secondary endpoints: radiographic response rate, PFS, PSA PFS, and toxicity.

Main Results:

• The trial enrolled 30 patients between January 2021 and June 2024, with early termination due to poor accrual.
• Primary endpoint achieved in 60% of the 177Lu-PSMA-617 arm vs. 13% in the control arm (Risk Ratio: 4.5, P=0.008).
• Objective radiographic response rates were 53% vs. 7% (P=0.014). Median radiographic PFS was 18 months vs. 9 months. No grade 3/4 toxicity observed with 177Lu-PSMA-617.

Conclusions:

• 177Lu-PSMA-617 consolidation therapy demonstrated promising efficacy and safety in mHSPC patients with residual disease after chemohormonal treatment.
• The treatment led to significantly higher PSA response and improved radiographic PFS.
• Larger phase 3 trials are warranted to confirm survival benefits.