title: Efficacy of Cabazitaxel in Castration-resistant Prostate Cancer Is Independent of the Presence of AR-V7 in Circulating Tumor Cells.
abstract: BACKGROUND
  Androgen receptor splice variant 7 (AR-V7) in circulating tumor cells (CTCs) from patients with metastatic castration-resistant prostate cancer (mCRPC) was recently demonstrated to be associated with resistance to abiraterone and enzalutamide. Cabazitaxel might, however, remain effective in AR-V7-positive patients.
  
  
  OBJECTIVE
  To investigate the association between AR-V7 expression in CTCs and resistance to cabazitaxel.
  
  
  METHODS
  We selected patients with mCRPC from the multicenter, randomized, phase 2, randomized, open-label, multicenter study in mCRPC on the pharmacodynamic effects of budesonide on cabazitaxel (Jevtana) (CABARESC). Before the start of the first and third cabazitaxel cycle, CTCs were enumerated using the CellSearch System. In patients with ≥10 CTCs in 7.5 ml blood at baseline, the expression of AR-V7 was assessed by quantitative polymerase chain reaction.
  
  
  METHODS
  The primary end point was the association between the AR-V7 status and the CTC response rate (decrease to fewer than five CTCs in 7.5 ml blood during treatment). Secondary end points were the prostate-specific antigen (PSA) response rate (RR) and overall survival (OS). Analyses were performed using chi-square and log-rank tests.
  
  
  CONCLUSIONS
  AR-V7 was detected in 16 of 29 patients (55%) with ≥10 CTCs and was more frequently found in abiraterone pretreated patients (5 of 5 [100%] treated vs 7 of 20 [35%] untreated; p=0.009). We found no differences in CTC and PSA RRs. The presence of AR-V7 in CTCs was not associated with progression-free survival (hazard ratio [HR]: 0.8; 95% confidence interval [CI], 0.4-1.8) or overall survival (HR 1.6; 95% CI, 0.6-4.4).
  
  
  CONCLUSIONS
  The response to cabazitaxel seems to be independent of the AR-V7 status of CTCs from mCRPC patients. Consequently, cabazitaxel might be a valid treatment option for patients with AR-V7-positive CTCs.
  
  
  RESULTS
  Tools are needed to select specific treatments for specific patients at specific times. The presence of the gene AR-V7 in CTCs has been associated with resistance to anti-androgen receptor treatments. We investigated whether this holds true for cabazitaxel, but we found cabazitaxel to be effective independent of the presence of AR-V7.
authors.affiliation: Erasmus Medical Center Cancer Institute and Cancer Genomics Netherlands, Department of Medical Oncology, Rotterdam, The Netherlands. Electronic address: w.onstenk@erasmusmc.nl.
authors.forename: Wendy
authors.initials: W
authors.lastname: Onstenk
authors.affiliation: Erasmus Medical Center Cancer Institute and Cancer Genomics Netherlands, Department of Medical Oncology, Rotterdam, The Netherlands.
authors.forename: Anieta M
authors.initials: AM
authors.lastname: Sieuwerts
authors.affiliation: Erasmus Medical Center Cancer Institute and Cancer Genomics Netherlands, Department of Medical Oncology, Rotterdam, The Netherlands.
authors.forename: Jaco
authors.initials: J
authors.lastname: Kraan
authors.affiliation: Erasmus Medical Center Cancer Institute and Cancer Genomics Netherlands, Department of Medical Oncology, Rotterdam, The Netherlands.
authors.forename: Mai
authors.initials: M
authors.lastname: Van
authors.affiliation: Erasmus Medical Center Cancer Institute and Cancer Genomics Netherlands, Department of Medical Oncology, Rotterdam, The Netherlands.
authors.forename: Annemieke J M
authors.initials: AJ
authors.lastname: Nieuweboer
authors.affiliation: Erasmus Medical Center Cancer Institute and Cancer Genomics Netherlands, Department of Medical Oncology, Rotterdam, The Netherlands.
authors.forename: Ron H J
authors.initials: RH
authors.lastname: Mathijssen
authors.affiliation: Sint Franciscus Gasthuis, Department of Internal Medicine, Rotterdam, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Hamberg
authors.affiliation: Gelre Ziekenhuizen, Department of Internal Medicine, Zutphen, The Netherlands.
authors.forename: Hielke J
authors.initials: HJ
authors.lastname: Meulenbeld
authors.affiliation: GZA Hospitals Saint Augustinus, Wilrijk, Belgium; Center for Oncological Research, University of Antwerp, Antwerp, Belgium.
authors.forename: Bram
authors.initials: B
authors.lastname: De Laere
authors.affiliation: GZA Hospitals Saint Augustinus, Wilrijk, Belgium; Center for Oncological Research, University of Antwerp, Antwerp, Belgium.
authors.forename: Luc Y
authors.initials: LY
authors.lastname: Dirix
authors.affiliation: Erasmus MC, Department of Urology, Rotterdam, The Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: van Soest
authors.affiliation: Erasmus Medical Center Cancer Institute and Cancer Genomics Netherlands, Department of Medical Oncology, Rotterdam, The Netherlands.
authors.forename: Martijn P
authors.initials: MP
authors.lastname: Lolkema
authors.affiliation: Erasmus Medical Center Cancer Institute and Cancer Genomics Netherlands, Department of Medical Oncology, Rotterdam, The Netherlands.
authors.forename: John W M
authors.initials: JW
authors.lastname: Martens
authors.affiliation: Erasmus MC, Department of Urology, Rotterdam, The Netherlands.
authors.forename: Wytske M
authors.initials: WM
authors.lastname: van Weerden
authors.affiliation: Erasmus MC, Department of Urology, Rotterdam, The Netherlands.
authors.forename: Guido W
authors.initials: GW
authors.lastname: Jenster
authors.affiliation: Erasmus Medical Center Cancer Institute and Cancer Genomics Netherlands, Department of Medical Oncology, Rotterdam, The Netherlands.
authors.forename: John A
authors.initials: JA
authors.lastname: Foekens
authors.affiliation: Erasmus Medical Center Cancer Institute and Cancer Genomics Netherlands, Department of Medical Oncology, Rotterdam, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: de Wit
authors.affiliation: Erasmus Medical Center Cancer Institute and Cancer Genomics Netherlands, Department of Medical Oncology, Rotterdam, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sleijfer
mesh_terms: D000368:Aged; D006801:Humans; D008297:Male; D009360:Neoplastic Cells, Circulating / Q000737:chemistry; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology*; D011944:Receptors, Androgen / Q000032:analysis; D043823:Taxoids / Q000627:therapeutic use*
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen; D043823:Taxoids; C552428:cabazitaxel
keywords: AR-V7; Androgen receptor; Cabazitaxel; Castration-resistant prostate cancer; CellSearch; Circulating tumor cells; Metastatic prostate cancer