ENZA-p
Combining ¹⁷⁷Lu-PSMA-617 with enzalutamide, and using PSMA PET to select and adapt
Quick Answer
ENZA-p (Emmett et al., Lancet Oncology 2024; ANZUP 1901) was a phase 2 randomized trial that tested adding ¹⁷⁷Lu-PSMA-617 to enzalutamide versus enzalutamide alone in men with high-risk, first-line mCRPC. The combination improved PSA progression-free survival, and later analyses reported overall-survival and quality-of-life benefits. Its distinctive design used PSMA PET (with an adaptive number of ¹⁷⁷Lu-PSMA cycles guided by imaging response) and selected high-risk patients by PSMA-avidity — an early model for combination and imaging-adaptive radioligand therapy.
The trial
Design: open-label, randomized phase 2, 162 patients with first-line mCRPC at high risk of early progression (selected by clinical factors and ⁶⁸Ga-PSMA-11 + FDG PET). Randomized to enzalutamide plus ¹⁷⁷Lu-PSMA-617 versus enzalutamide alone; the number of ¹⁷⁷Lu-PSMA cycles was adaptive, guided by interim PSMA PET response. Primary endpoint: PSA progression-free survival.
Key result
The combination improved PSA-PFS (≈13 vs 7.8 months; HR ≈ 0.43) versus enzalutamide alone, with higher PSA response rates. Secondary analyses reported longer overall survival and better quality of life with the combination, and toxicity was manageable (expected PSMA-therapy effects such as dry mouth and cytopenias). The adaptive, PET-guided dosing supported tailoring cycle number to imaging response.
Why it mattered
ENZA-p is an early randomized demonstration that combining radioligand therapy with an androgen-receptor pathway inhibitor can outperform the ARPI alone in first-line mCRPC, and that PSMA PET can both select patients and adapt therapy (cycle number driven by imaging response). It points toward combination, biomarker-adaptive radioligand strategies rather than fixed-course monotherapy.
Context & caveats
ENZA-p is a phase 2 trial with PSA-PFS as the primary endpoint; the OS and quality-of-life findings come from secondary/updated analyses and warrant phase 3 confirmation. Enrollment was enriched for high-risk, PSMA-avid disease, so results should not be generalized to unselected or PSMA-low populations.
Self-Check
Q1. What did ENZA-p test, and in whom?
Answer: ¹⁷⁷Lu-PSMA-617 plus enzalutamide vs enzalutamide alone in first-line, high-risk, PSMA-avid mCRPC.
Q2. What made its design distinctive?
Answer: PSMA-PET selection and adaptive dosing — the number of ¹⁷⁷Lu-PSMA cycles was guided by interim PSMA PET response.
Q3. What was the primary result?
Answer: Improved PSA progression-free survival (≈13 vs 7.8 months; HR ≈ 0.43); later analyses reported OS and quality-of-life benefit.
Q4. What is the main caveat?
Answer: It is a phase 2 trial in an enriched high-risk PSMA-avid population; OS/QoL are secondary findings needing phase 3 confirmation.
Key References
- Emmett L, et al. [¹⁷⁷Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial. Lancet Oncol 2024;25:563–571. doi:10.1016/S1470-2045(24)00135-9
Evidence & sources
https://nuc.med/enza-p-trial/ Report an issue