PSMAfore
¹⁷⁷Lu-PSMA-617 before chemotherapy, moving radioligand therapy earlier in mCRPC
Quick Answer
PSMAfore (Morris et al., Lancet 2024) was the phase 3 randomized trial that tested ¹⁷⁷Lu-PSMA-617 in taxane-naïve mCRPC — patients who had progressed on one androgen-receptor pathway inhibitor (ARPI) but had not yet received chemotherapy. Compared with switching to a second ARPI, ¹⁷⁷Lu-PSMA-617 significantly prolonged radiographic progression-free survival, supporting a pre-chemotherapy role for PSMA radioligand therapy and extending the VISION population earlier in the disease course.
The trial
Design: phase 3, open-label, randomized trial of 468 patients with PSMA-positive mCRPC who had progressed on one ARPI and were taxane-naïve (chemotherapy not yet indicated/declined). Randomized to ¹⁷⁷Lu-PSMA-617 versus a change of ARPI (abiraterone↔enzalutamide). Primary endpoint: radiographic progression-free survival (rPFS); crossover from the ARPI arm to ¹⁷⁷Lu-PSMA-617 was permitted at progression.
Key result
¹⁷⁷Lu-PSMA-617 roughly doubled rPFS (≈12 vs 5–6 months; HR ≈ 0.4) with higher PSA and objective response rates and a favorable, better-tolerated safety profile versus the ARPI switch. Overall survival was confounded by extensive crossover (most control patients crossed to ¹⁷⁷Lu-PSMA-617), so OS did not reach a clear separation — the durable signal was the rPFS and quality-of-life advantage.
Why it mattered
PSMAfore provided randomized evidence that ¹⁷⁷Lu-PSMA-617 is effective before chemotherapy — earlier than its VISION (post-taxane) indication — giving patients a radioligand option when the alternative is often a low-yield second ARPI switch. It is a key trial in the ongoing shift of PSMA therapy earlier in the mCRPC treatment sequence.
Context & caveats
Interpretation of overall survival is limited by high crossover, a common issue when the control therapy is less effective and ethical crossover is allowed. Eligibility required PSMA-positive disease on PSMA PET (with limits on PSMA-negative/discordant lesions), so appropriate imaging selection remains essential.
Self-Check
Q1. What population and comparison defined PSMAfore?
Answer: Taxane-naïve, PSMA-positive mCRPC after one ARPI — ¹⁷⁷Lu-PSMA-617 versus switching to a second ARPI.
Q2. What was the primary result?
Answer: ¹⁷⁷Lu-PSMA-617 roughly doubled radiographic PFS (≈12 vs 5–6 months; HR ≈ 0.4) versus the ARPI change.
Q3. Why was overall survival hard to interpret?
Answer: Extensive crossover — most control patients crossed over to ¹⁷⁷Lu-PSMA-617 at progression, diluting any OS separation.
Q4. How does PSMAfore relate to VISION?
Answer: VISION supported ¹⁷⁷Lu-PSMA-617 post-taxane; PSMAfore extends the evidence to a pre-chemotherapy (taxane-naïve) population — moving PSMA therapy earlier.
Key References
- Morris MJ, et al. [¹⁷⁷Lu]Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naïve patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial. Lancet 2024;404:1227–1239. doi:10.1016/S0140-6736(24)01653-2
Evidence & sources
https://nuc.med/psmafore-trial/ Report an issue