CABA-V7: a prospective biomarker selected trial of cabazitaxel treatment in AR-V7 positive prostate cancer patients.

Background: Metastatic castration-resistant prostate cancer (mCRPC) patients with positive AR-V7 expression in their circulating tumour cells (CTCs) rarely derive benefit from abiraterone and enzalutamide.
Design: We performed a prospective, multicenter, single arm phase II clinical trial (CABA-V7) in mCRPC patients previously treated with docetaxel and androgen deprivation therapy.
Objective: In this trial, we investigated whether cabazitaxel treatment resulted in clinically meaningful PSA response rates in patients with positive CTC-based AR-V7 expression and collected liquid biopsies for genomic profiling.
Results: Cabazitaxel was found to be modestly effective, with only 12% of these patients obtaining a PSA response. Genomic profiling revealed that CTC-based AR-V7 expression was not associated with other known mCRPC-associated alterations. CTC-based AR-V7 status and dichotomised CTC counts were observed as independent prognostic markers at baseline.
Conclusions: AR-V7 positivity predicted poor overall survival (OS). However, cabazitaxel-treated AR-V7 positive patients and those lacking AR-V7 positivity, who received cabazitaxel as standard of care, appeared to have similar OS. Therefore, despite the low response rate, cabazitaxel may still be an effective treatment in this poor prognosis, AR-V7 positive patient population.
Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ronald de Wit has acted in a consulting or advisory role for Sanofi, Merck, Astellas, Bayer, Orion; and has received research funding from Bayer, Sanofi, Travel support from Sanofi, Bayer. Stefan Sleijfer has acted in a consulting or advisory role for the Center for Personalized Cancer Treatment (chair), Dutch Science Agenda Personalized Medicine (chair) and Supervisory board of SkylineDx; and holds an interest in patent #10555926 (Use of cabazitaxel in the treatment of prostate cancer) held by Erasmus University Medical Center Rotterdam. Martijn P. Lolkema has acted in a consulting or advisory role for Sanofi, Johnson & Johnson, Merck, Astellas, Incyte, Amgen, Janssen Cilag, Bayer, Servier and Pfizer. John. W. M. Martens has acted in a consulting or advisory role for Novartis. Paul Hamberg has acted in a consulting or advisory role for Astellas, MSD, Pfizer AstraZeneca, BMS, Ipsen. Bianca Mostert has acted in consulting or advisory role for Servier, BMS and Lilly; and has received research funding from Sanofi, BMS. Ron H.J. Mathijssen acted in a consulting or advisory role Servier; and has received research funding for Sanofi, Pamgene, Astellas, ISI, Bayer, Servier, Roche, Novartis, Cristal Therapeutics, and Pfizer. All remaining authors have declared no conflicts of interest.
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