ASCO GU 2021: CTC Counts as a Biomarker of Prognosis and Response in Metastatic Castration-Resistant Prostate Cancer (mCRPC) from the CARD Trial

(UroToday.com) There have been many advances in the field of systemic therapy for advanced prostate cancer in the past 15 years. While, prior to the publication of TAX-327, there were no available treatments with proven life-prolonging benefits, we now have many treatments available with demonstrable improvements in overall survival. Thus, we now face the question of how to sequence these agents. In the prospective CARD trial (NCT02485691), cabazitaxel treatment demonstrated significantly improved progression-free survival (rPFS) and overall survival (OS) compared to abiraterone acetate or enzalutamide among patients with metastatic castration resistant prostate cancer (mCRPC) who had previously received docetaxel and progressed within 12 months of starting the alternative androgen-axis inhibitor.


Despite these advances, there remains a dearth of data for biomarkers of prognosis and response to treatment. In a poster presentation at the 2021 ASCO GU Cancers Symposium, Dr. Johann De Bono and colleagues presented their work assessing the role of circulating tumor cell (CTC) counts as a biomarker of prognosis and response to therapy, among patients enrolled to the CARD trial.

To do so, the authors utilized blood samples collected at the time of screening, on cycle 2 day 1, and at the end of therapy. These samples then underwent analysis for CTC analysis. The authors pre-specified CTC to be any cytokeratin-positive, CD45-negative cells.

CD45-negative_cells.png

The authors then tested the association between CTC counts and time-to-event endpoints (rPFS and OS) and categorical outcomes (objective tumor response) using multivariable Cox models and chi-squared tests, respectively.

Among 255 patients randomized within the CARD trial, 237 (93%) had evaluable samples at screening and 213 (84%) had evaluable samples on day 1 of cycle 2. At least one CTC were detected in 204 samples (86%) at screening at 178 samples (84%) at cycle 2 with the median number of CTCs of 4.1 (interquartile range 1.3-14.2) and 5.2 (IQR 1.5-17.3) at each time point respectively.

From baseline assessment performed at the time of screening, higher CTC counts were associated with other poor prognostic factors including higher levels of lactate dehydrogenase (p=0.014), alkaline phosphatase (p<0.001), and prostate specific antigen (p<0.001). Further, measured continuously, higher CTC counts were independent with poorer overall survival (p=0.03) but not differences in rPFS (p=0.7). Similarly, when dichotomized around the median, there was improved OS for patients with low CTC counts but no difference in rPFS.

CTC_counts.png

Considering next the change in absolute CTC count from the screening visit to cycle 2, the authors found that (including patients in both treatment arms), there was a benefit in terms of pRFS for patients who had favourable changes in CTC count. Additionally, conversion from high to low or maintenance of low CTC counts was associated with objective tumor response.

CARD_trial.png

Further, clearance of high-CK expressing cells was associated with improved rPFS (p=0.006) and OS (p=0.005). This was more commonly observed among patients who received cabazitaxel.

high-CK_expressing.png

In summary, the authors conclude that this pre-planned analysis of the CARD trial demonstrates that baseline CTC counts are prognostic among patients undergoing third-line systemic therapy for mCRPC. Further, early favourable changes in CTC status (ie. conversion to undetectable) are associated with the response to therapy. Ongoing work will assess whether CTC changes may be used as a surrogate for survival, thus allowing early outcome ascertainment. Further, analysis of the associations of CTC subtypes including androgen receptor variant 7, chromosomal instability, heterogeneity, small-cell/neuroendocrine morphology is ongoing.

Presented by: Johann de Bono, MB ChB FRCP MSc Ph.D. FMedSci. Professor Johann de Bono is Regius Professor of Cancer Research and a Professor in Experimental Cancer Medicine at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center Contact: @WallisCJD on Twitter during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021


Related Content:

Clinical Trial Information: NCT02485691
email news signup