# Chromosomal instability in circulating tumor cells and cabazitaxel resistance in metastatic castration-resistant prostate cancer

## TL;DR

This study shows that chromosomal instability in circulating tumor cells can predict resistance to chemotherapy in prostate cancer patients.

## Contribution

It confirms CTC-CIN as a predictive biomarker for taxane resistance in metastatic castration-resistant prostate cancer.

## Key findings

- High baseline CTC-CIN counts were linked to worse overall survival in mCRPC patients.
- Detectable CTC-CIN at baseline predicted lack of benefit from cabazitaxel compared to ARPI.
- CTC-CIN is a clinically useful biomarker for taxane resistance in mCRPC.

## Abstract

Predictive biomarkers to guide chemotherapy decisions for metastatic castration–resistant prostate cancer (mCRPC) are lacking. Preclinical studies indicate that circulating tumor cell (CTC) studies of chromosomal instability (CTC-CIN) can predict taxane resistance.

The CARD trial randomized individuals with mCRPC progressing within a year of treatment with an androgen receptor pathway inhibitor (ARPI; enzalutamide or abiraterone acetate plus prednisolone/prednisone) to cabazitaxel or the alternative ARPI. As a preplanned biomarker analysis, CTCs were isolated from blood samples obtained at baseline, cycle 2, and the end of treatment. Associations between baseline CTC and CTC-CIN 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 were assessed.

High baseline CTC-CIN counts 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). Detectable CTC-CIN counts at baseline may predict a lack of ibPFS and OS benefit when comparing cabazitaxel with ARPI.

This preplanned analysis of biomarker data from the CARD trial confirms that CTC-CIN counts are a clinically useful prognostic and predictive biomarker of taxane resistance in mCRPC. Detectable CTC-CIN at baseline defines a patient subpopulation with unmet clinical needs in which alternative therapeutics should be tested.

ClinicalTrials.gov number NCT02485691.

Funded by Sanofi and Epic Sciences.

In this sub-analysis of a landmark clinical trial, circulating tumor cells with features of chromosomal instability predicts resistance to chemotherapy in prostate cancer patients.