Enzalutamide plus LuPSMA has enhanced anticancer effects in prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer.
Both the nonsteroidal antiandrogen enzalutamide and the PSMA-specific radionucleotide treatment lutetium-177-PSMA-617 (LuPSMA) improve overall survival (OS) in mCRPC.1,2 It is known that treatment with enzalutamide upregulates PSMA expression in tumor cells. Therefore, combining enzalutamide and LuPSMA could be synergistic, a hypothesis that was tested in the randomized phase 2 ENZa-p trial (NCT04419402).
A total of 162 participants with mCRPC, rising prostate-specific antigen (PSA) levels, at least 2 high-risk factors for early enzalutamide failure, and a positive gallium 68 PSMA scan were randomized 1:1 to enzalutamide or enzalutamide plus LuPSMA. LuPSMA was given 15 days after the start of enzalutamide and 6 weeks later. Participants in the LuPSMA arm who had maintained a positive PSMA scan at day 92 were offered 2 extra LuPSMA doses. The primary endpoint is PSA-progression-free survival (PSA-PFS). Secondary endpoints include radiological PFS (rPFS), PSA50% and PSA90% response rates (PSA50RR, PSA90RR), adverse events, and OS.
Results from the first interim analysis at a median follow-up of 20 months were presented by Dr. Louise Emmett of St Vincent’s Hospital Sydney, Australia.3 LuPSMA favored PSA-PFS, the primary endpoint. Median PSA-PFS was 13 months in the LuPSMA arm versus 7.8 months in the enzalutamide alone arm (HR, 0.43; 95% CI, 0.29-0.63; P<.00001). PSA response rates were also in favor of LuPSMA, where PSA50RR was 93% in the LuPSMA arm versus 67% in the enzalutamide arm. PSA90RR was 78% versus 37%. Adverse events were similar in both arms.
“These results provide strong evidence that the combination of enzalutamide and LuPSMA has enhanced anticancer effects in PSMA-positive mCRPC patients,” Dr. Emmett concluded. “In addition, the adaptive LuPSMA-dosing has the potential to reduce toxicity by only administering in patients with persistent PSMA-avid disease.” Progression-free and overall survival data are planned for July 2024.
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