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Poster session 10

1365P - The impact of PSMA-positive circulating tumor cells in men with metastatic castrate-resistant prostate cancer (mCRPC)

Date

10 Sep 2022

Session

Poster session 10

Topics

Cancer Biology;  Pathology/Molecular Biology;  Translational Research;  Targeted Therapy;  Molecular Oncology;  Survivorship

Tumour Site

Neuroendocrine Tumours;  Prostate Cancer

Presenters

Santosh Gupta

Citation

Annals of Oncology (2022) 33 (suppl_7): S616-S652. 10.1016/annonc/annonc1070

Authors

S. Gupta1, Q. Yang2, S. Halabi3, A. Tubbs4, Y. Gore1, D.J. George5, D.M. Nanus6, E.S. Antonarakis7, D. Danila8, R. Szmulewitz9, R.J. Wenstrup10, A.J. Armstrong11

Author affiliations

  • 1 Translational Research, Epic Sciences Inc., 92121 - San Diego/US
  • 2 Department Of Biostatistics And Bioinformatics, Duke University Medical Center, 27710 - Durham/US
  • 3 Biostatistics And Bioinformatics, Duke University - Health System, 27710 - Durham/US
  • 4 Medical Office, Epic Sciences Inc., 92121 - San Diego/US
  • 5 Dept. Medical Oncology, Duke University Medical Center, NC 27710 - Durham/US
  • 6 Medicine, Weill Cornell Medical College, 10065 - New York/US
  • 7 Medical Oncology, Johns Hopkins University, 21231 - Baltimore/US
  • 8 Gu Medical Oncology Department, MSKCC - Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 9 Hematology / Oncology, The University of Chicago Medical Centre, 60653 - Chicago/US
  • 10 Translational Research, Epic Sciences, 92121 - San Diego/US
  • 11 Medicine, Duke Cancer Center, 27710 - Durham/US
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Abstract 1365P

Background

PSMA-targeted radioligand therapy has dramatically improved outcomes in mCRPC men. A liquid biopsy assay to detect and characterize PSMA expression and heterogeneity could be helpful to guide optimal therapy and identify patients most likely to benefit.

Methods

We conducted a retrospective analysis of the multicenter PROPHECY trial of mCRPC men (n=118) treated with abiraterone (abi) or enzalutamide (enza). CTCs were utilized to quantify PSMA protein expression and heterogeneity prior to therapy and at progression using a validated immunofluorescent method. Associations of PSMA+ CTC enumeration with overall survival (OS) and radiographic progression-free survival (rPFS) were explored using Cox modeling. We described changes in expression prevalence over time, and association with AR-V7 and neuroendocrine phenotypes.

Results

97 men had evaluable samples for CTC PSMA detection at baseline, with 80% of men having at least 1 CTC (n=78). Of these men, 55% (43/78) had PSMA expression on CTCs and 21% (16/78) had ≥2 PSMA+ CTCs+ (optimal cut-off); 19% had complete PSMA homogeneity (100% expression). At progression on abi/enza, 88% (50/57) of men had ≥1 detectable CTC, of whom 68% (34/50) were CTC PSMA+ CTCs, and 12% had 100% PSMA+ CTCs. PSMA+ CTC expression increased with progression on abi/enza (n=29, 34% vs 17%) with the majority of PSMA+CTC (>50%) vs. pre-treatment expression, respectively. The median OS for CTC 0 (reference category), PSMA-CTC, PSMA+CTC: 26, 21 and 11 mo, respectively. In univariate analyses, PSMA+ CTC were adversely prognostic for both OS (hazard ratio (HR)=3.4; 95% CI=1.6-7.0) and rPFS (HR=2.8, 95% CI=1.4-5.8). Adjusting for prior therapy, Halabi risk score, and CTC, HRs for OS and rPFS PSMA+ CTC+ was 3.0 (95% CI=1.1-7.8) and 2.3 (95% CI=0.9-5.8). We observed PSMA expression heterogeneity regardless of CTC NEPC or AR-V7 phenotype.

Conclusions

We quantified PSMA CTC heterogeneity in mCRPC men before and following progression on abi/enza therapy, finding an increase in PSMA CTC detection following progression on AR therapy. CTC and PSMA CTC enumeration are adversely prognostic, and this assay could be useful to select patients appropriate for PSMA targeted therapies.

Clinical trial identification

PROPHECY (NCT02269982) Recruitment Status: Completed First Posted: October 21, 2014 Last Update Posted: June 10, 2019.

Editorial acknowledgement

Legal entity responsible for the study

Andrew J Armstrong.

Funding

Prostate Cancer Foundation.

Disclosure

S. Gupta: Other, Institutional, Full or part-time Employment: Epic Sciences Inc. S. Halabi: Financial Interests, Personal, Other, Member of DSMB: Sanofi, Aveo Oncology; Financial Interests, Institutional, Funding: ASCO. A. Tubbs: Other, Institutional, Full or part-time Employment: Epic Sciences Inc. Y. Gore: Other, Institutional, Full or part-time Employment: Epic Sciences. Inc. D.J. George: Financial Interests, Personal, Other, Consultant: Advanced Accelerator Applications SA/Novartis, Aveo Pharmaceuticals, Eisai, IdeoOncology, Merck Sharp & Dohme, Myovant Sciences, Inc., Propella Therapeutics, RevHealth, LLC, Seattle Genetics, WebMD, Xcures; Financial Interests, Personal, Other, Sr. Editor: American Association for Cancer Research; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board, CAPI-281 Steering Committee member: AstraZeneca; Financial Interests, Personal, Invited Speaker, and Consultant: Bayer H/C Pharmaceuticals, Exelixis, Inc; Financial Interests, Personal, Other, Consultant/IDMC member: Janssen Pharmaceuticals; Financial Interests, Personal, Other, Contributor: Medscape Education; Financial Interests, Personal, Other, Honorarium, Consultant: Michael J Hennessey Associates; Financial Interests, Personal, Other, Co-Editor-in-Chief: Millennium Medical Publishing, Clinical Advances in Hematology & Oncology; Financial Interests, Personal, Other, Steering Committee member: NCI Genitourinary (Leidos biomedical Research); Financial Interests, Personal, Other, Consultant, Steering Committee member, Honorarium: Pfizer; Financial Interests, Personal, Other, Consultant, Speaker, Honorarium: Sanofi; Financial Interests, Personal, Other, Honorarium: UroGPO; Financial Interests, Personal, Other, Honorarium, Travel Accommodations: UroToday; Financial Interests, Personal, Expert Testimony: WilmerHale Attorneys; Financial Interests, Institutional, Funding: Astellas, AstraZeneca, Bristol Myers Squibb, Calithera, Exelisix, Janssen Pharmaceuticals, Novartis, Pfizer, Sanofi. D.M. Nanus: Other, Personal and Institutional, Funding: AstraZeneca. E.S. Antonarakis: Financial Interests, Personal, Advisory Role: Janssen, Astellas, Sanofi, Dendreon, Pfizer, Amgen, AstraZeneca, Bristol Myers Squibb, Clovis, Merck; Financial Interests, Institutional, Funding: Janssen, Johnson & Johnson, Sanofi, Dendreon, Genentech, Novartis, Tokai, Bristol Myers-Squibb, AstraZeneca, Clovis, Merck; Financial Interests, Personal and Institutional, Royalties, co-inventor of a biomarker technology that has been licensed to Qiagen: Qiagen. D. Danila: Non-Financial Interests, Personal, Other: ANGLE, Pfizer, Aximmune, Clovis Oncology, Janssen Scientific Affairs, LLC, Astellas Pharma; Financial Interests, Personal, Other: ANGLE; Financial Interests, Personal, Advisory Role: Sanador, Pfizer, Clovis Oncology, BioView; Financial Interests, Personal and Institutional, Funding: PCF Foundation; Financial Interests, Institutional, Funding: Janssen Research & Development, Amgen, Biosplice; Financial Interests, Personal and Institutional, Royalties: Gene expression profile associated with PCa. R. Szmulewitz: Other, Personal, Other: Astellas Pharma, Pfizer; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Advisory Role: Exelixis, Merck, Amgen, Janssen Oncology, Sanofi, Astellas Pharma, Pfizer; Financial Interests, Institutional, Funding: AbbVie, Astellas Pharma, Macrogenics, Janssen Oncology, Plexxikon, Harpoon therapeutics, Merck, Novartis; Financial Interests, Institutional, Royalties, Patent licensed by University of Chicago of which I am co-inventor to Corcept Therapeutics for combination AR/GR inhibition in prostate cancer: University of Chicago; Financial Interests, Personal and Institutional, Other: Corcept Therapeutics. R.J. Wenstrup: Financial Interests, Institutional, Full or part-time Employment: Epic Sciences Inc. A.J. Armstrong: Financial Interests, Personal, Advisory Role: BMS, Merck, Pfizer, AstraZeneca, Forma, Exelixis, Myovant, Dendreon, Clovis, Epic Sciences, Exact Sciences, Janssen, Bayer; Financial Interests, Institutional, Funding: BMS, Merck, Pfizer, AstraZeneca, Forma, Exelixis, Myovant, Dendreon, Clovis, Genentech/Roche, Amgen, Janssen, Bayer. All other authors have declared no conflicts of interest.

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