Randomized phase 2 study of [¹⁷⁷Lu]-PSMA-617 versus standard of care for oligometastatic hormone-sensitive prostate cancer

¹⁷⁷Lu-PSMA-617 is a novel treatment for metastatic castration-resistant prostate cancer. The randomized phase 2 BULLSEYE trial, at three centers in The Netherlands and one center in Cyprusm evaluated ¹⁷⁷Lu-PSMA-617 in patients with PSMA-expressing oligometastatic hormone-sensitive prostate cancer (HSPC). Eligible patients were adult men with biochemically recurrent HSPC after radical prostatectomy or radiotherapy, an ECOG performance status 0 or 1, a PSA doubling time of lessthan 6months, and PSA over 1.0 μg/L. Patients were randomized 1:1 to ¹⁷⁷Lu-PSMA-617 (intervention; n=29) or standard of care (control) of deferred androgen deprivation therapy (n=29). Co-primary endpoints were the proportion of patients with disease progression, and time to disease progression.The median follow-up time was 27 months (IQR 18-32). During the first 30 weeks, disease progression was reporte in 7% of patients in the intervention group and 93% of patients in the control group, with median progression-free survival of 25 months versus 5 months (HR 0.07; p<0.0001). One patient in the intervention group developed grade 3 dry eyes, and grade 3 lymphocyte count decrease was observed in three patients (10%) in the treatment group. There were no grade 4 or 5 treatment-related adverse events. The authors conclude that ¹⁷⁷Lu-PSMA-617 showed promising response rates and delayed disease progression in patients with oligometastatic HSPC, with most treatment-related adverse events being low grade.