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

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

Yoon Ji Choi  1 , Hye Sook Kim  1 , Se Hoon Park  2 , Bong-Seog Kim  3 , Kyoung Ha Kim  4 , Hyo Jin Lee  5 , Hong Suk Song  6 , Dong-Yeop Shin  7   8 , Ha Young Lee  9 , Hoon-Gu Kim  10 , Kyung Hee Lee  11 , Jae Lyun Lee  2 , Kyong Hwa Park  1
Affiliations
Clinical Trial

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

Yoon Ji Choi et al. Cancer Res Treat. 2018 Oct.

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.

PubMed Disclaimer

Conflict of interest statement

We thank Novartis for their kind donation of dovitinib for this study.

Figures

Fig. 1.
Fig. 1.
Progression-free survival (PFS) (A) and overall survival (OS) (B). Dashed lines are the upper bound and lower bound of 95% confidence interval of Kaplan-Meier estimates.
Fig. 2.
Fig. 2.
Progression-free survival (PFS) according to history of chemotherapy. CI, confidence interval.
Fig. 3.
Fig. 3.
Duration of clinical benefit.
Fig. 4.
Fig. 4.
Biomarker levels at baseline and after two cycles of dovitinib. (A) Fibroblast growth factor receptor 2 (FGFR2) levels. (B) Vascular endothelial growth factor receptor 2 (VEGFR2) levels.
Fig. 5.
Fig. 5.
Progression-free survival (PFS) according to baseline vascular endothelial growth factor receptor 2 (VEGFR2) levels. CI, confidence interval.
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