Regorafenib in antiangiogenic-naive, chemotherapy-refractory advanced colorectal cancer: A phase IIb trial.

Abstract

782 Background: The oral multikinase inhibitor regorafenib improves overall survival in advanced colorectal cancer (CRC). The aim of this study was to investigate the safety and efficacy of regorafenib in antiangiogenic-naïve patients with chemotherapy-refractory CRC. Methods: In this single-center, single-arm, phase 2b study, patients received regorafenib 160 mg/day for 3 weeks on/1 week off. Tumor response assessed by RECIST 1.1 and tumor metabolic response by [18F] fluorodeoxyglucose positron emission tomography (PET/CT) according to the European Organization for Research and Treatment of Cancer (EORTC) criteria were evaluated at week 8 (W8). PFS rate was defined as the percentage of evaluable patients alive without progression at W8. Safety was assessed until the cut-off date (May 2, 2017). Results: Overall, 59 patients (59.3% male; median age 58.0 yrs) received regorafenib (median dose 148.8 mg/day). The W8 PFS rate was 46.6% (95% CI 33.3% - 60.1%) and median PFS and OS were 3.6 and 7.5 months, respectively. Overall disease control rate (DCR) was 50.8% by RECIST and 62.7% by EORTC criteria (Table). Most common regorafenib-related grade ≥3 AEs were hypertension (35.6%), hand-foot skin reaction (HFSR) (25.4%) and hypophosphatemia (22.0%). One patient discontinued treatment due to drug-related HFSR. Conclusions: The W8 PFS rate and overall DCR support the anti-tumor activity of regorafenib in antiangiogenic-naïve, chemotherapy-refractory advanced CRC. Compared with the previous phase 3 CORRECT and CONCUR trials, the median PFS suggests a better outcome in this population. These data provide the basis for further investigation of regorafenib’s role in earlier treatment lines in metastatic CRC and on the use of PET/CT in tumor response assessment. Clinical trial information: NCT02465502. [Table: see text]