A phase II study of apatinib, a highly selective inhibitor of VEGFR-2, in patients with metastatic solid tumors without standard treatment options

Abstract

Background: VEGFR‐2 signaling has a pivotal role in tumor angiogenesis. Apatinib (YN968D1) is a highly selective tyrosine kinase inhibitor of VEGFR‐2. A previous phase I study of continuous daily dosing of apatinib in solid tumors identified 850 mg per day as the recommended dose (Sharma et al., 2015 ASCO). This study was a phase II trial evaluating the preliminary efficacy and safety of apatinib in advanced solid tumors. Methods: In Korea and the US, 30 patients ( pts) with metastatic GC (n = 15), CRC (n = 9), NSCLC (n = 3), NET (n = 2) or mesothelioma (n = 1) who failed standard chemotherapy received apatinib 850 mg p.o. q.d. until disease progression or unacceptable toxicity. Other key eligibility criteria included presence of measurable lesions and an ECOG performance status <2. Results: Among the 30 pts, 21 pts (70.0%) were male, and the median age was 56.5 years (range, 32‐82). Twenty‐three pts (76.7%) were Asian, and the remaining 7 pts (23.3%) were Caucasian. In 28 evaluable pts, partial response (PR) was noted in 3 pts (10.7%, 1 GC, 1 NSCLC, and 1 NET), and stable disease (SD) in 23 pts (82.1%) with a disease control rate (DCR) of 92.9% at 8 weeks. All 15 GC pts were evaluable with 1 PR (6.7%), 12 SD (80.0%), and 2 cases of progressive disease (PD) (13.3%), resulting in a DCR of 86.7%. Grade > 3 adverse events observed in more than 5% of pts included hypertension (n = 7), increased blood bilirubin (n = 4), hypokalemia (n = 3) and hand‐foot skin reaction (HFSR) (n = 2). Toxicities were generally well tolerated, and there was no toxicity‐related death. Conclusions: Apatinib showed a promising anti‐tumor activity in advanced solid tumors after failure of standard treatment, and was well tolerated with manageable toxicity profiles. The results of this study support further investigation of apatinib in solid tumors, especially in gastric cancer in which efficacy and safety of apatinib has been reported in a Chinese phase 3 study.