Abstract 7582: Descriptive analysis of patients with mCRPC and liver metastases receiving alpha and beta PSMA targeted radionuclide therapy (PSMA-TRT)

Abstract Introduction: Predictors of outcomes after PSMA-TRT are still being established. Liver metastases (mets) have been associated with poor response. Mutations in genes encoding DNA damage repair (DDR) and TP53 affect radiosensitivity. Here we describe a cohort of patients with mCRPC and liver metastases treated on clinical trials of PSMA-TRT. Methods: 39 patients with liver mets were enrolled on phase I/II PSMA-TRT studies between Jan 2006 to Apr 2022. Patients received alpha therapy (225Ac-J591), beta therapy (fractionated 177Lu-PSMA-617, single-dose and fractionated 177Lu-J591) or a combination of both (225Ac-591 and 177Lu-PSMA-I patients enrolled after 2017 had PSMA-PET imaging. 15 patients also had genomic analysis completed. Results: Median age was 69 (range 55-93), PSA 85. 7 (2. 45-9614). 39 (100%) bone mets, 33 (84. 6%) LN, 9 (23. 1%) lung. 22 (56. 4%) greater than 1 ARPI, 23 (59. 0%) greater thanc 1 chemo, 13 (33. 3%) sip-T, 7 (17. 9%) Ra-223, 4 (10. 2%) prior TRT (with concurrent liver mets). Of the 19 with both CT and PSMA PET, 18 (94. 7%) were identified on PSMA PET (including 8 PET only), 10 (55. 6%) on CT (1 CT only, i. e. non-PSMA PET avid). Median whole body PSMA-imaging score (PSMA-IS) was 4 (range 1-4), with 7 (17. 9%) 1-2 and 32 (82. 1%) 3-4. 9 (23. 0%) received alpha-TRT, 26 (66. 7%) beta-TRT, and 4 (10. 3%) combo-TRT. Somatic or germline analysis was completed in 15 (38. 5%) of 39 patients. 8 (53. 3%) had mutations in DNA repair pathways (3 in BRCA2, 3 in CHEK 2, 1 in FANC, 1 in MSH2). 7 (46. 7%) had mutations in TP53. 31 patients (79. 5%) had PSA decline, with 15 (38. 5%) achieving PSA 50. 26 (66. 7%) had baseline CTC measured; 19 (73. 0%) had detectable CTC at baseline. Of these 19, 3 (15. 8%) converted to undetectable after therapy and 2 (10. 5%) converted to favorable CTC. PSA50 rate in alpha-TRT was 4 (44. 4%), beta-TRT 8 (30. 7%), combo-TRT 3 (75%). PSA50 in patients with PSMA-IS 1-2 was 1 (14. 2%) compared to 14 (43. 9%) in PSMA-IS 3-4. 3 (37. 5%) of 8 patients with mutDDR achieved PSA50, compared to 3 (42. 9%) with mutTP53. Conclusions: This dataset adds to the collective literature of two subgroups of patients with mCRPC receiving TRT: those with liver disease and those with mutations in DNA repair pathways. The results of this study suggest higher rates of response in patients receiving alpha therapy, either alone or in combination with beta therapy, and in patients with high radiotracer uptake on PSMA-PET, based on PSMA-imaging score of 3 or 4. Genomic alterations in DRR proteins did not have clear implications. Citation Format: Samuel Ruder, Michael Sun, Andres Ricaurte Fajardo, Jones Nauseef, Zachary Davidson, Joseph Thomas, Sandra Huicochea Castellanos, Ana Molina, Cora Sternberg, Amie Patel, Escarleth Fernandez, Sarah Yuan, Edward Fung, Vasilios Avlonitis, Elisabeth O'Dwyer, David Nanus, Joseph Osborne, Neil Bander, Scott Tagawa. Descriptive analysis of patients with mCRPC and liver metastases receiving alpha and beta PSMA targeted radionuclide therapy (PSMA-TRT) abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 7582.