Abstract 1145: Morphological evaluation of chromosomal instability in circulating tumor cells and prediction of taxane resistance in metastatic prostate cancer: a prespecified sub-analysis of the CARD trial

Abstract Background: Chromosomal instability (CIN) is frequent in patients with metastatic castration-resistant prostate cancer (mCRPC) and determines taxane resistance. A circulating tumor cell (CTC) assay which morphologically identifies CTCs with CIN (CTC-CIN) from a single tube of whole blood could predict clinical outcomes in this population. We tested this hypothesis as a pre-planned, secondary outcome of the CARD trial, where patients with mCRPC progressing within a year of treatment with an androgen receptor pathway inhibitor (ARPI; enzalutamide or abiraterone acetate + prednisolone/prednisone) were randomized to treatment with cabazitaxel or the alternative ARPI. Methods: CTCs were isolated from blood samples obtained at baseline; cycle two, and end of treatment. The associations of baseline CTC and counts with imaging-based progression free survival (ibPFS), overall survival (OS), time to prostate-specific antigen (PSA) progression, RECIST 1.1 objective response rate (ORR), and PSA50 response rate (PRR) were assessed. Results: Of 255 patients randomized, CTC counts were acquired from 237 patients at screening, 213 patients at C2D1, and 166 patients at EOT. High baseline CTC counts were significantly associated with worse OS (median OS, 14.9 vs 9.8 months; univariate HR, 1.81; 95% CI, 1.30 - 2.51; p < 0.001). High baseline CTC-CIN counts were significantly associated with worse OS after adjustment for confounding variables (median OS, 15.3 vs 8.9 months; univariate HR, 2.16; 95% CI, 1.52 - 3.06; p < 0.001; multivariate HR, 1.56; 95% CI, 1.01 - 2.43; p = 0.047). Low CTC-CIN at baseline predicted ibPFS, ORR, and PRR benefit with cabazitaxel; conversely, high at baseline predicted no different ibPFS or OS outcomes with cabazitaxel or a second ARPI. Conclusions: This preplanned biomarker analysis of CARD confirmed that CTC-CIN counts are prognostic for OS and may be predictive of cabazitaxel benefit. (Funded by Sanofi and Epic Sciences; CARD ClinicalTrials.gov number, NCT02485691.) Citation Format: Ossian Longoria, Jan Rekowski, Santosh Gupta, Nick Beije, Klaus Pantel, Eleni Efstathiou, Cora Sternberg, Daniel Castellano, Karim Fizazi, Bertrand Tombal, Adam Sharp, Oliver Sartor, Sandrine Mace, Christine Geffriaud-Ricouard, Richard Wenstrup, Ronald de Wit, Johann de Bono. Morphological evaluation of chromosomal instability in circulating tumor cells and prediction of taxane resistance in metastatic prostate cancer: a prespecified sub-analysis of the CARD trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1145