TOPLINE:

[¹⁷⁷Lu]-prostate-specific membrane antigen-617 (¹⁷⁷Lu-PSMA-617) delayed disease progression in patients with oligometastatic hormone-sensitive prostate cancer, with median progression-free survival of over 2 years in patients receiving this treatment vs 5 months in patients receiving standard of care.

METHODOLOGY:

• Researchers conducted an open-label, randomised, phase 2 trial at three academic hospitals in Netherlands and one community hospital in Cyprus, including 58 adult men with biochemically recurrent prostate cancer following radical prostatectomy or radiotherapy.
• Patients were randomly assigned in a 1:1 ratio to receive ¹⁷⁷Lu-PSMA-617 (intervention group; n = 29; median age, 69 years) or standard of care consisting of deferred androgen deprivation therapy with active monitoring (control group; n = 29; median age, 72 years).
• Patients in the intervention group received two cycles of 7.4 GBq ¹⁷⁷Lu-PSMA-617 administered 6 weeks apart; those with residual PSMA-expressing disease on PSMA-PET-CT and no grade ≥ 3 treatment-related adverse events were eligible for two additional cycles.
• Primary endpoints were disease progression and time to disease progression (progression-free survival), assessed between study groups at 30 weeks.
• Secondary endpoints included time to initiation of next systemic therapy, prostate-specific antigen (PSA) progression per the Phoenix criteria, time to development of castration-resistant prostate cancer (CRPC), and a ≥ 50% decrease in PSA levels.

TAKEAWAY:

• Disease progression was observed in 7% of patients in the intervention group and 93% of patients in the control group during the first 30 weeks. Median progression-free survival was 25 months in the intervention group vs 5 months in the control group (hazard ratio [HR], 0.07; P < .0001).
• Median time to next systemic therapy was 26 months in the intervention group vs 6 months in the control group (HR, 0.09; P < .0001). PSA progression-free survival was greater in the intervention group than in the control group (17 months vs 3 months; P < .0001).
• Among patients treated with ¹⁷⁷Lu-PSMA-617, 83% achieved a ≥ 50% decline in PSA levels. CRPC developed in five patients in the intervention group and four patients in the control group.
• Treatment-related adverse events were predominantly grade 1-2, occurring as dry mouth in 66% of patients, fatigue in 55%, and nausea in 48%; one patient developed grade 3 dry eyes, and three experienced grade 3 decreases in lymphocyte count, with no treatment-related grade 4 adverse events or deaths.

IN PRACTICE:

"These findings suggest that following surgery and radiotherapy, ¹⁷⁷Lu-PSMA-617 might provide an additional treatment option for patients with oligometastatic HSPC [hormone-sensitive prostate cancer]," the authors wrote.

SOURCE:

The study was led by Bastiaan M. Privé, MD, Department of Radiology and Nuclear Medicine, Radboud University Medical Centre, Nijmegen, Netherlands. It was published online in April in Issue 4 of Volume 27 of The Lancet Oncology.

LIMITATIONS:

The study was limited by its small sample size and the selection criterion of a PSA doubling time of 6 months or less. The primary endpoint of disease progression was not a validated surrogate endpoint. The crossover design, which allowed patients in the control group to receive ¹⁷⁷Lu-PSMA-617 upon progression, prevented the assessment of overall survival and the time to CRPC. Lastly, lead-time bias may have been introduced.

DISCLOSURES:

The study was funded by the Dutch Prostate Cancer Foundation (Prostaatkankerstichting) and Novartis. Five authors reported receiving research grants, consulting fees, or honoraria from Novartis or various other sources. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.