Association between DNA damage repair alterations and outcomes to ¹⁷⁷Lu-PSMA-617 in advanced prostate cancer.

This showed a trend toward poorer outcomes among patients with a tumor-only DDR alteration [PSA50: adjusted OR 0.29 (0.10-0.78), P = 0.02; PSA-PFS: adjusted HR 1.65 (0.95-2.87), P = 0.07; OS: adjusted HR 1.51 (0.73-3.10), P = 0.26].

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Olaparib led to a PSA50 rate of 43% among all patients with DDR alterations in the PROFOUND trial, with a PSA50 of 62% among those with BRCA alterations 15 ; in our study, while the PSA50 among all patients with DDR alterations was similar (38%), the PSA50 for those with BRCA2 alterations was 46% and there was a clear trend (albeit non-significant) toward poorer outcomes (PSA-PFS, OS) with LuPSMA in DDR-altered patients.

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