TheraP
¹⁷⁷Lu-PSMA-617 versus cabazitaxel, and the dual PSMA/FDG selection that defined it
Quick Answer
TheraP (Hofman et al., Lancet 2021; ANZUP 1603) was a phase 2 randomized trial that compared ¹⁷⁷Lu-PSMA-617 with cabazitaxel in men with docetaxel-treated mCRPC. ¹⁷⁷Lu-PSMA-617 produced a higher PSA response rate with fewer severe toxicities. Its most influential feature was patient selection by dual ⁶⁸Ga-PSMA-11 and FDG PET — enrolling PSMA-avid disease and excluding PSMA-negative/FDG-positive (discordant) disease — which crystallized the dual-tracer selection concept.
The trial
Design: open-label phase 2, 200 patients with progressive mCRPC after docetaxel, screened with dual PSMA and FDG PET (PSMA-avid, without significant FDG-discordant disease). Randomized to ¹⁷⁷Lu-PSMA-617 versus cabazitaxel. Primary endpoint: PSA response (≥50% decline).
Key result
PSA response was higher with ¹⁷⁷Lu-PSMA-617 (≈66% vs 37%), with fewer grade 3–4 adverse events than cabazitaxel. Progression-free survival favored ¹⁷⁷Lu-PSMA-617; overall survival was similar between arms on later analysis (both are active therapies, and crossover occurred). The headline for practice was comparable-or-better efficacy with a better toxicity profile versus a standard chemotherapy.
Why it mattered
TheraP positioned ¹⁷⁷Lu-PSMA-617 as an effective, better-tolerated alternative to cabazitaxel, complementing VISION's survival evidence. Uniquely, it operationalized dual-tracer (PSMA + FDG) screening — the standard way to identify discordant, target-negative disease that PSMA therapy would miss — making the mismatch concept a practical selection tool.
Context & caveats
TheraP was a phase 2 trial with PSA response (not survival) as the primary endpoint, and its dual-tracer selection makes its population somewhat enriched. Its OS equivalence with cabazitaxel is interpreted alongside VISION's OS benefit versus standard of care.
Self-Check
Q1. What did TheraP compare, and what was the primary result?
Answer: ¹⁷⁷Lu-PSMA-617 vs cabazitaxel in docetaxel-treated mCRPC; ¹⁷⁷Lu-PSMA-617 gave a higher PSA response (≈66% vs 37%) with fewer severe toxicities.
Q2. What selection method makes TheraP distinctive?
Answer: Dual ⁶⁸Ga-PSMA-11 and FDG PET screening — enrolling PSMA-avid disease and excluding PSMA-negative/FDG-positive (discordant) disease.
Q3. How did overall survival compare between arms?
Answer: Similar OS (both are active therapies; crossover occurred) — the advantage was higher PSA response and better tolerability, not an OS difference.
Q4. How does TheraP complement VISION?
Answer: VISION showed an OS benefit vs standard of care; TheraP showed ¹⁷⁷Lu-PSMA-617 is an effective, better-tolerated alternative to cabazitaxel and formalized dual-tracer selection.
Key References
- Hofman MS, et al. [¹⁷⁷Lu]Lu-PSMA-617 versus cabazitaxel in mCRPC (TheraP): a randomised, open-label, phase 2 trial. Lancet 2021;397:797–804. doi:10.1016/S0140-6736(21)00237-3
Evidence & sources
https://nuc.med/therap-trial/ Report an issue