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

2022; Elsevier BV; Volume: 177; Linguagem: Inglês

10.1016/j.ejca.2022.09.032

1879-0852

Khrystany T. Isebia, Bianca Mostert, Bodine P.S. Belderbos, Stefan A.J. Buck, Jean C. A. Helmijr, Jaco Kraan, Corine M. Beaufort, Mai N. Van, Esther Oomen‐de Hoop, Anieta M. Sieuwerts, Wilfred F. J. van IJcken, Mirjam C.G.N. van den Hout - van Vroonhoven, Rutger W. W. Brouwer, Edwin Oole, Paul Hamberg, Brigitte C.M. Haberkorn, Helgi H. Helgason, Ronald de Wit, Stefan Sleijfer, Ron H.J. Mathijssen, John W.M. Martens, Maurice P.H.M. Jansen, Job van Riet, Martijn P. Lolkema,

PARP inhibition in cancer therapy

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.We performed a prospective, multicenter, single arm phase II clinical trial (CABA-V7) in mCRPC patients previously treated with docetaxel and androgen deprivation therapy.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.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.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.