title: Changes in plasma biomarkers following treatment with cabozantinib in metastatic castration-resistant prostate cancer: a post hoc analysis of an extension cohort of a phase II trial.
abstract: BACKGROUND
  Cabozantinib is an orally available inhibitor of tyrosine kinases including VEGFR2 and c-MET. We performed a post hoc analysis to find associations between select plasma biomarkers and treatment response in patients (pts) with metastatic castration resistant prostate cancer (mCRPC) who received cabozantinib 100 mg daily as part of a phase 2 non-randomized expansion cohort (NCT00940225).
  
  
  METHODS
  Plasma samples were collected at baseline, 6 weeks and at time of maximal response from 81 mCRPC pts with bone metastases, of which 33 also had measurable soft-tissue disease. Levels of 27 biomarkers were measured in duplicate using enzyme-linked immunosorbent assay. Spearman correlation coefficients were calculated for the association between biomarker levels or their change on treatment and either bone scan response (BSR) or soft tissue response according to RECIST.
  
  
  RESULTS
  A BSR and RECIST response were seen in 66/81 pts (81 %) and 6/33 pts (18 %) respectively. No significant associations were found between any biomarker at any time point and either type of response. Plasma concentrations of VEGFA, FLT3L, c-MET, AXL, Gas6A, bone-specific alkaline phosphatase, interleukin-8 and the hypoxia markers CA9 and clusterin significantly increased during treatment with cabozantinib irrespective of response. The plasma concentrations of VEGFR2, Trap5b, Angiopoietin-2, TIMP-2 and TIE-2 significantly decreased during treatment with caboznatinib.
  
  
  CONCLUSIONS
  Our data did not reveal plasma biomarkers associated with response to cabozantinib. The observed alterations in several biomarkers during treatment with cabozantinib may provide insights on the effects of cabozantinib on tumor cells and on tumor micro-environment and may help point to potential co-targeting approaches.
authors.affiliation: Department of Oncology, Sheba Medical Center, Tel Hashomer, Israel. Raya.leibowitz-amit@sheba.health.gov.il.
authors.forename: Raya
authors.initials: R
authors.lastname: Leibowitz-Amit
authors.affiliation: Division of Biostatistics, Princess Margaret Cancer Center, University Health Network, Toronto, Canada. melania.pintilie@uhn.ca.
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, 610 University Ave, Toronto, ON, M5G 2M9, Canada. Leila.khoja@uhn.ca.
authors.forename: Leila
authors.initials: L
authors.lastname: Khoja
authors.affiliation: Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada. arun.azad@bccancer.cn.ca.
authors.forename: Arun A
authors.initials: AA
authors.lastname: Azad
authors.affiliation: Department of Oncology, Sheba Medical Center, Tel Hashomer, Israel. raanan.berger@sheba.heath.gov.il.
authors.forename: Raanan
authors.initials: R
authors.lastname: Berger
authors.affiliation: Exelixis, Inc, South San Francisco, CA, USA. dlaird@exelixis.com.
authors.forename: A Douglas
authors.initials: AD
authors.lastname: Laird
authors.affiliation: Exelixis, Inc, South San Francisco, CA, USA. daftab@exelixis.com.
authors.forename: Dana T
authors.initials: DT
authors.lastname: Aftab
authors.affiliation: Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada. kchi@bccancer.bc.ca.
authors.forename: Kim N
authors.initials: KN
authors.lastname: Chi
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, 610 University Ave, Toronto, ON, M5G 2M9, Canada. Anthony.joshua@uhn.ca.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Joshua
mesh_terms: D000813:Anilides / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D011725:Pyridines / Q000627:therapeutic use*; D015203:Reproducibility of Results; D018709:Statistics, Nonparametric
chemical_list: D000813:Anilides; D014408:Biomarkers, Tumor; D011725:Pyridines; C558660:cabozantinib