CTC and AR-V7 analysis in the ECOG-ACRIN 8153 (CHAARTED2) randomized trial: Abiraterone (Abi) with or without cabazitaxel (Abi-Cabazi) in extensive mCRPC following docetaxel

Christos Kyriakopoulos; Yu-Hui Chen; Robert Jeraj; Fenghai Duan; Abhishek Tripathi; David Kosoff; Rohan Garje; Russell Kent Pachynski; Rahul Atul Parikh; Andrea Harzstark; Nabil Adra; Benjamin L. Maughan; Yousef Zakharia; Paul Gettys Corn; Glenn Liu; Michael A Carducci; Jun Luo; Emmanuel S. Antonarakis

doi:10.1200/JCO.2025.43.5_suppl.181

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CTC and AR-V7 analysis in the ECOG-ACRIN 8153 (CHAARTED2) randomized trial: Abiraterone (Abi) with or without cabazitaxel (Abi-Cabazi) in extensive mCRPC following docetaxel

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CTC and AR-V7 analysis in the ECOG-ACRIN 8153 (CHAARTED2) randomized trial: Abiraterone (Abi) with or without cabazitaxel (Abi-Cabazi) in extensive mCRPC following docetaxel

Christos Kyriakopoulos, Yu-Hui Chen, Robert Jeraj, Fenghai Duan, Abhishek Tripathi, David Kosoff, Rohan Garje, Russell Kent Pachynski, Rahul Atul Parikh, Andrea Harzstark, …

Journal of clinical oncology, Vol.43(5_suppl), pp.181-181

02/10/2025

DOI: 10.1200/JCO.2025.43.5_suppl.181

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Abstract

181 Background: The CHAARTED2 trial showed improved PFS with Abi-Cabazi over Abi-alone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) who previously received docetaxel for metastatic castration-sensitive disease. Here, we evaluated the prognostic and predictive impact of CTC and AR-V7 circulating biomarkers. Methods: The modified AdnaTest (Qiagen) was used to define CTC detection (+ vs –) and AR-V7 detection (+ vs –) at baseline, C5D1, as well as at the time of progression. We first assessed the prognostic value of baseline and C5D1 CTC and AR-V7 status in the two arms. We also assessed the predictive potential of baseline and C5D1 CTC and AR-V7 status to explore if these biomarkers may aid in treatment selection. Logrank test and Cox proportional hazards models were used to assess for associations between clinical outcomes and baseline biomarker status. Landmark analysis was performed to evaluate associations at C5D1. Results: A total of 223 pts were randomized between the two arms. CTC data were evaluable for 94/112 and 94/111 pts in the Abi-alone and Abi-Cabazi arms, respectively. Baseline CTC detection was prognostic for worse PFS in both the Abi-alone (7.1 vs 31.7 months, HR 3.64, P <0.001) and the Abi-Cabazi (9.6 vs 36.9 months, HR 4.13, P <0.001) arms. Likewise, baseline AR-V7 detection portended worse PFS in the Abi-alone (4.1 vs 12.8 months, HR 3.34, P <0.001) and the Abi-Cabazi (6.9 vs 15.1 months, HR 3.17, P <0.001) arms. At C5D1, there was a higher rate of CTC(-) conversion (60 vs 46%) and AR-V7(-) conversion (69 vs 58%) in the Abi-Cabazi arm. CTC(-) and AR-V7(-) status at C5D1 was prognostic of improved PFS in both arms (all P ≤0.02). In terms of predictive impact, PFS was numerically but not statistically longer in the Abi-Cabazi arm in all biomarker groups; the greatest relative PFS benefit to Abi-Cabazi was in the baseline AR-V7(+) group (HR 0.68, 95%CI 0.36–1.3, P =0.2). Similarly, at C5D1, the greatest relative PFS benefit to Abi-Cabazi was in pts remaining AR-V7(+) (HR 0.57, 95%CI 0.15–2.16, P =0.4). Conclusions: Baseline CTC and AR-V7 detection were both prognostic for inferior PFS in both study arms. PFS outcomes were broadly longer in the Abi-Cabazi vs Abi-alone arm in all biomarker groups. The presence of AR-V7 at baseline and at C5D1 was the strongest relative predictor of Abi-Cabazi benefit, but did not meet statistical significance. Clinical trial information: NCT03419234 .

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Title: Subtitle: CTC and AR-V7 analysis in the ECOG-ACRIN 8153 (CHAARTED2) randomized trial: Abiraterone (Abi) with or without cabazitaxel (Abi-Cabazi) in extensive mCRPC following docetaxel
Creators: Christos Kyriakopoulos - University of Wisconsin Carbone Cancer Center
Yu-Hui Chen - Dana-Farber Cancer Institute
Robert Jeraj - University of Wisconsin–Madison
Fenghai Duan - Brown University
Abhishek Tripathi - City Of Hope National Medical Center
David Kosoff - University of Wisconsin Carbone Cancer Center
Rohan Garje - Baptist Hospital of Miami
Russell Kent Pachynski - Washington University in St. Louis
Rahul Atul Parikh - The University of Kansas Cancer Center
Andrea Harzstark - Kaiser Permanente San Francisco Medical Center
Nabil Adra - Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Benjamin L. Maughan - University of Utah
Yousef Zakharia - University of Iowa
Paul Gettys Corn - The University of Texas MD Anderson Cancer Center
Glenn Liu - University of Wisconsin Carbone Cancer Center
Michael A Carducci - Sidney Kimmel Comprehensive Cancer Center
Jun Luo - Johns Hopkins University
Emmanuel S. Antonarakis - University of Minnesota
Resource Type: Abstract
Publication Details: Journal of clinical oncology, Vol.43(5_suppl), pp.181-181
DOI: 10.1200/JCO.2025.43.5_suppl.181
ISSN: 0732-183X
eISSN: 1527-7755
Publisher: LIPPINCOTT WILLIAMS & WILKINS; PHILADELPHIA
Grant note: National Cancer InstituteGenzyme CorporationSanofi S.A
National Cancer Institute; Genzyme Corporation, a subsidiary of Sanofi S.A.
Language: English
Date published: 02/10/2025
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984792372702771

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