732P - A phase II study of TKI258 in patients with castration-resistant prostate cancer (KCSG-GU11-05)

Abstract

FGF signals are important in carcinogenesis and progression of prostate cancer. TKI258 (dovitinib) is an oral, pan-class VEGFR, PDGFR, and FGFR inhibitor. Preclinical data demonstrated a significant activity of TKI258 in mouse xenograft models. We evaluated the efficacy and toxicity of TKI258 in men with metastatic CRPC. This study was a single-arm, phase II, open-label, multicenter trial of TKI258 (500mg orally according to a 5-days-on and 2-days-off schedule). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and PSA response rate. Biomarker analyses for serum FGFR, FGF-23 and VEGFR using multiplex ELISA were performed. This study is registered with ClinicalTrials.gov, number NCT01741116. Forty-four men were accrued from 11 hospitals: 80% post-docetaxel; median PSA was 100 ng/dl, median age was 69, 82% had bone metastases, 23% had liver metastases. Median cycles of TKI258 was 2 (range 0-33). Median PFS was 3.67 months (95% CI: 1.36-5.98) and median OS was 13.7 months (95% CI: 0-27.41). Chemotherapy-naïve patients had longer PFS (17.9 months, 95% CI, 9.23-28.57) compared with docetaxel-treated patients (2.07 months, 95% CI, 1.73-2.41, p = 0.001) and the patients with high serum VEGFR2 level over median level (7800 pg/ml) showed longer PFS compared with others. (6.03 [95% CI, 4.26-7.80] vs 1.97 [95% CI, 1.79-2.15] months, p = 0.023). The PSA decline was observed in 32.3% and 12.9% of patients achieved a > 50% decline. Four objective responses were observed with ORR of 12.5% (95% CI: 5.0-28.1%). Grade 3 related AEs were seen in 40.9% of patients with 7.0% stopping TKI258 due to toxicity. The most common related AEs included grade 1-2 nausea, diarrhea, fatigue, anorexia and all grade thrombocytopenia (29.5%). TKI258 showed modest antitumor activity with manageable toxicities in men with mCRPC. Especially, patients who were chemo-naïve or with high levels of serum VEGFR2 had the benefit from TKI258.