Background
Phase II open-label RCT (ANZUP TheraP) of 200 men with metastatic castration-resistant prostate cancer who had progressed after docetaxel and for whom cabazitaxel was the next appropriate standard treatment; eligibility required PSMA-avid disease on Ga-68 PSMA-11 PET and no discordant FDG-PET-positive sites.
Interventions and follow up
Arm A: 177Lu-PSMA-617 6.0-8.5 GBq IV q6wk for up to 6 cycles
Arm B: Cabazitaxel 20 mg/m2 IV q3wk for up to 10 cycles
Primary endpoint: PSA response rate (≥50% reduction)
Median follow up: 18.4 mo
Arm B: Cabazitaxel 20 mg/m2 IV q3wk for up to 10 cycles
Primary endpoint: PSA response rate (≥50% reduction)
Median follow up: 18.4 mo
Results
PSA response rate (ITT): 66% vs 37% (A vs B); difference 29% (95% CI 16-42); P<.0001
PSA response rate (treated population): 66% vs 44% (A vs B); difference 23% (95% CI 9-37); P=.0016
PSA response rate (treated population): 66% vs 44% (A vs B); difference 23% (95% CI 9-37); P=.0016
Adverse events
Grade 3-4 events: 33% vs 53% (A vs B)
Hematologic: Thrombocytopenia 11% vs 0%; neutropenia 4% vs 13%; febrile neutropenia 0% vs 8%
Other: Dry mouth common with arm A; oral hydration encouraged on treatment days
Hematologic: Thrombocytopenia 11% vs 0%; neutropenia 4% vs 13%; febrile neutropenia 0% vs 8%
Other: Dry mouth common with arm A; oral hydration encouraged on treatment days
Conclusions
177Lu-PSMA-617 produced higher PSA response, fewer grade 3-4 adverse events, and improved patient-reported outcomes versus cabazitaxel in men with mCRPC progressing after docetaxel. Updated analyses showed similar overall survival between arms.
Key Limitations
Phase II, open-label, with PSA response (not survival) as the primary endpoint; PSMA/FDG PET selection enriched for responders, limiting generalizability. Final survival analyses showed no OS difference between arms.
Clinical Context
TheraP provided the first randomized comparison of 177Lu-PSMA-617 against cabazitaxel, complementing the placebo-controlled VISION trial that supported FDA/EMA approval. Together they inform ASCO/ESMO positioning of PSMA-targeted radioligand therapy in PSMA-avid mCRPC.