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Data from PSMA-positive Circulating Tumor Cell Detection and Outcomes with Abiraterone or Enzalutamide Treatment in Men with Metastatic Castrate-resistant Prostate Cancer

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Gupta, S; Halabi, S; Yang, Q; Roy, A; Tubbs, A; Gore, Y; George, DJ; Nanus, DM; Antonarakis, ES; Danila, DC; Szmulewitz, RZ; Wenstrup, R ...
April 4, 2023

<div>AbstractPurpose:<p>In men with metastatic castration-resistant prostate cancer (mCRPC), prostate-specific membrane antigen (PSMA)-targeted radioligand therapy has drastically improved clinical outcomes. A liquid biopsy characterizing PSMA expression could be useful in guiding optimal therapy.</p>Experimental Design:<p>We conducted a retrospective analysis of the prospective multicenter PROPHECY (Prospective CiRculating PrOstate Cancer Predictors in HighEr Risk mCRPC StudY) trial of men with mCRPC (<i>n</i> = 118) treated with abiraterone (abi) or enzalutamide (enza). Circulating tumor cells (CTC) were enriched (CTC/mL) and characterized for PSMA protein expression/heterogeneity at baseline and progression. We utilized proportional hazards modeling of the association between PSMA-positive (PSMA+) CTC enumeration with overall survival (OS) and progression-free survival (PFS).</p>Results:<p>Overall, 97 men with mCRPC had evaluable blood samples for baseline CTC PSMA detection; 78 men (80%) had detectable CTCs. Of these, 55% (43/78) of men had any PSMA CTC detection, 21% (16/78) had ≥2 PSMA+ CTCs/mL, and 19% (8/43) were 100% PSMA+. At progression on abi/enza, 88% (50/57) of men had detectable CTCs, 68% (34/50) had any PSMA CTCs, and 12% (4/34) had 100% PSMA+ CTCs. Among paired cases (<i>n</i> = 57), PSMA+ CTC detection increased slightly after abi/enza progression. Using an optimal cutoff of ≥2 PSMA+ CTCs/mL, median OS was 26, 21, and 11 months for men without CTCs, PSMA− CTCs, and PSMA+ CTCs. Adjusting for prior abi/enza therapy, Halabi clinical risk score, and CTC enumeration, the HRs for OS and PFS for PSMA+ CTC+ were 3.0 [95% confidence interval (CI) = 1.1–7.8] and 2.3 (95% CI = 0.9–5.8).</p>Conclusions:<p>We observed PSMA CTC heterogeneity between and within patients with mCRPC over time during abi/enza progression. CTC PSMA enumeration was adversely prognostic independent of clinical factors and disease burden. Further validation is warranted in the context of PSMA-targeted therapies.</p></div>

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Publication Date

April 4, 2023
 

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Gupta, S., Halabi, S., Yang, Q., Roy, A., Tubbs, A., Gore, Y., … Armstrong, A. J. (2023). Data from PSMA-positive Circulating Tumor Cell Detection and Outcomes with Abiraterone or Enzalutamide Treatment in Men with Metastatic Castrate-resistant Prostate Cancer. https://doi.org/10.1158/1078-0432.c.6516198.v2
Gupta, Santosh, Susan Halabi, Qian Yang, Akash Roy, Alisa Tubbs, Yamini Gore, Daniel J. George, et al. “Data from PSMA-positive Circulating Tumor Cell Detection and Outcomes with Abiraterone or Enzalutamide Treatment in Men with Metastatic Castrate-resistant Prostate Cancer,” April 4, 2023. https://doi.org/10.1158/1078-0432.c.6516198.v2.
Gupta S, Halabi S, Yang Q, Roy A, Tubbs A, Gore Y, George DJ, Nanus DM, Antonarakis ES, Danila DC, Szmulewitz RZ, Wenstrup R, Armstrong AJ. Data from PSMA-positive Circulating Tumor Cell Detection and Outcomes with Abiraterone or Enzalutamide Treatment in Men with Metastatic Castrate-resistant Prostate Cancer. 2023.

DOI

Publication Date

April 4, 2023