Phase II Study of Dovitinib in Patients with Castration-Resistant Prostate Cancer (KCSG-GU11-05)

Cancer Res Treat. 2018 Oct;50(4):1252-1259. doi: 10.4143/crt.2017.438. Epub 2018 Jan 2.

Abstract

Purpose: Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC).

Materials and methods: This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500 mg/day (5-days-on/2-days-off schedule). The primary endpointwas 16-week progression-free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and prostate-specific antigen (PSA) response rate. Biomarker analyses for VEGFR2, FGF23, and FGFR2 using multiplex enzyme-linked immunosorbent assay was performed.

Results: Forty-four men were accrued from 11 hospitals. Eighty percent were post-docetaxel. Median PSA was 100 ng/dL, median age was 69, 82% had bone metastases, and 23% had liver metastases. Median cycles of dovitinibwas 2 (range, 0 to 33). Median PFSwas 3.67 months (95% confidence interval [CI], 1.36 to 5.98) and median OS was 13.70 months (95% CI, 0 to 27.41). Chemotherapy-naïve patients had longer PFS (17.90 months; 95% CI, 9.23 to 28.57) compared with docetaxel-treated patients (2.07 months; 95% CI, 1.73 to 2.41; p=0.001) and the patients with high serum VEGFR2 level over median level (7,800 pg/mL) showed longer PFS compared with others (6.03 months [95% CI, 4.26 to 7.80] vs. 1.97 months [95% CI, 1.79 to 2.15], p=0.023). Grade 3 related adverse events were seen in 40.9% of patients. Grade 1-2 nausea, diarrhea, fatigue, anorexia, and all grade thrombocytopenia are common.

Conclusion: Dovitinib showed modest antitumor activity with manageable toxicities in men with mCRPC. Especially, patients who were chemo-naïve benefitted from dovitinib.

Keywords: Biomarkers; Castration-Resistant Prostatic Neoplasm; Dovitinib.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Benzimidazoles / administration & dosage*
  • Benzimidazoles / adverse effects
  • Biomarkers, Tumor / metabolism*
  • Docetaxel / therapeutic use
  • Drug Administration Schedule
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / metabolism
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / metabolism
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Quinolones / administration & dosage*
  • Quinolones / adverse effects
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism
  • Survival Analysis
  • Treatment Outcome
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • 4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one
  • Benzimidazoles
  • Biomarkers, Tumor
  • FGF23 protein, human
  • Protein Kinase Inhibitors
  • Quinolones
  • Docetaxel
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • FGFR2 protein, human
  • KDR protein, human
  • Receptor, Fibroblast Growth Factor, Type 2
  • Vascular Endothelial Growth Factor Receptor-2