ESMO 2021: PSMAfore: A Phase 3 Study To Compare 177Lu-PSMA-617 Treatment With a Change in Androgen Receptor Pathway Inhibitor in Taxane-Naïve Patients With mCRPC

( In the on-demand poster session of the European Society for Medical Oncology (ESMO) Annual Congress, Dr. Morris provided a summary of the PSMAfore trial in progress (NCT04689828). This study examines the role of [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) in taxane-naïve patients with mCRPC. 177Lu-PSMA-617 is a high-affinity prostate-specific membrane antigen (PSMA)-targeted radioligand therapy that delivers β-particle radiation to cell expressing PSMA and the surrounding microenvironment. Among patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with ≥ 1 androgen receptor pathway inhibitor (ARPI) and 1–2 taxanes, the phase III VISION trial demonstrated that 177Lu-PSMA-617 significantly prolonged radiographic progression-free survival (rPFS) and overall survival. In the PSMAfore trial, Dr. Morris and colleagues are investigating the effect of 177Lu-PSMA-617 on rPFS in taxane-naïve patients with mCRPC treated with either 177Lu-PSMA-617 or a change in ARPI.

This is a multicentre, open-label, randomized phase III trial conducted in adult men with progressive mCRPC and confirmed PSMA expression by [68Ga]Ga-PSMA-11 PET/CT. In terms of prior treatment, to be eligible, patients must be taxane-naïve in the metastatic setting and have received one prior ARPI and be a candidate for a change in ARPI. Additionally, patients must have an ECOG performance status of 0 or 1; a castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L); and recovered to grade ≤ 2 from toxicities related to prior therapies.

The authors plan to randomize approximately 450 patients. After enrollment, patients will be randomized 1:1 to receive 177Lu-PSMA-617 (7.4 GBq i.v. every 6 weeks for 6 cycles) or a change in ARPI to either abiraterone or enzalutamide. Regardless of randomization, best supportive care is allowed in both arms. Randomization will be stratified according to prior ARPI use in castration-resistant vs hormone-sensitive prostate cancer settings and pain symptomatology (score 0–3 vs 4–10 on the worst pain intensity item of the Brief Pain Inventory – Short Form).


The authors will assess the primary endpoint of rPFS according to PCWG3-modified RECIST v1.1 criteria. Following blinded independent centrally confirmed radiographic progression, patients in the ARPI arm can crossover to the 177Lu-PSMA-617 arm.

The planned sample size of 450 patients provides 95% power to detect a hazard ratio of 0.56 for rPFS after 156 events with an overall one-sided significance level of 0.025. The key secondary endpoint is overall survival while other secondary endpoints include safety and tolerability of 177Lu-PSMA-617 and health-related quality of life.

Presented by: Michael Morris, MD, Prostate Cancer Section Head, Memorial Sloan Kettering Cancer Center, New York, New York, USA.