Abstract
Association of tumor genetics with outcomes in patients (pts) with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) treated with 177 Lu-PSMA-617
Journal of clinical oncology, Vol.42(16_suppl), pp.5050-5050
06/01/2024
DOI: 10.1200/JCO.2024.42.16_suppl.5050
Abstract
5050 Background: 177 Lu-PSMA-617 is approved for the treatment (tx) of mCRPC. Though tx is associated with improved survival, not all pts experience a benefit. Acquired resistance is common and some pts have intrinsic resistance. There is a lack of data on genomic markers that could aid in selecting pts for tx. In this study, we aim to characterize molecular predictors of benefit to 177 Lu-PSMA-617. Methods: We used the retrospective Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) clinical-genomic database (n=2100). The primary endpoint was to investigate the association of genomic alterations with a ≥50% PSA decline (PSA50) from baseline following 177 Lu-PSMA-617. Associations were assessed using Wald-chi square test and Cox regression in multivariable analysis. Secondary endpoints included clinical progression-free survival (PFS) and overall survival (OS). Results: We identified 115 pts with PSMA PET+ mCRPC treated with 177 Lu-PSMA-617 who had commercial genetic sequencing prior to tx (median age 72 yrs, 25% non-white). Median number of prior lines for mCRPC was 3 with 71 pts (62%) receiving >1 androgen receptor signaling inhibitor (ARSI) and 55 pts (48%) receiving >1 taxane; 11 pts (9%) received ARSI with 177 Lu-PSMA-617. Overall, the PSA50 was 49% with median OS and PFS of 14.0 and 7.6 months (mos), respectively. In pts with a PSA50, median OS and PFS were 22.6 and 11.6 mos, respectively, vs 11.2 and 5.6 mos for those without a PSA50. Genetic alterations associated with PSA50 are in the table. PSA50 was 48% in pts with (n=32) vs 49% in pts without DDR alterations (n=83). PSA50 was 44% in pts with tumor suppressor gene alterations (TSGa) ( PTEN, p53, RB1) (n=68) vs 56% in pts without (n=47). Median PFS was 7.6 vs 7.3 mos for pts with and without any TSGa (p=0.90), and median OS was 12.2 mos vs 22.6 mos for pts with and without TSGa (p=0.004). Of the 43 pts with AR alterations, 8/15 (53%) with LBD mutations, 10/27 (37%) with AR amplification, and 0/1 with AR-V7 had a PSA50. FGFR, CDK12 and MYC alterations were enriched in individuals without a PSA50 (75-83%). Conclusions: We demonstrate that CDK12, MYC and FGFR alterations were associated with a lower PSA50 with 177 Lu-PSMA-617. Larger cohorts should be investigated for confirmation, as biomarkers to inform relative benefit of tx could be useful in prioritizing options for mCRPC. [Table: see text]
Details
- Title: Subtitle
- Association of tumor genetics with outcomes in patients (pts) with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) treated with 177 Lu-PSMA-617
- Creators
- Justine Panian - University of California, San DiegoNicholas Henderson - University of Michigan–Ann ArborPedro C. Barata - University Hospitals Seidman Cancer CenterMehmet Asim Bilen - Emory UniversityLaura Graham - University of Colorado DenverElisabeth I. Heath - The Barbara Ann Karmanos Cancer InstituteDaniel Herchenhorn - D’Or Institute for Research and EducationClara Hwang - Henry Ford HospitalDeepak Kilari - Medical College of WisconsinVadim S Koshkin - University of California, San FranciscoJones T. Nauseef - Cornell UniversityAlexandra Sokolova - OHSU Knight Cancer InstituteYousef Zakharia - University of IowaMichael Thomas Schweizer - Fred Hutch Cancer CenterTanya B. Dorff - City Of Hope National Medical CenterAndrew J. Armstrong - Duke Medical CenterAjjai Shivaram Alva - University of Michigan–Ann ArborRana R. McKay - University of California, San Diego
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.42(16_suppl), pp.5050-5050
- DOI
- 10.1200/JCO.2024.42.16_suppl.5050
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Language
- English
- Date published
- 06/01/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984649156702771
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