ASCO 2013：一线治疗之Nintedanib对索拉非尼的头对头临床试验

Nintedanib是一个口服的酪氨酸激酶抑制剂，靶点包括VEGF、PDGF和FGF信号通路。在这个2期临床研究中，患者按照2:1的比例随机接受nintedanib或索拉非尼治疗，预期2013年年底可以获得研究结果。

Open-label, phase I/randomized, phase II trial of the triple angiokinase inhibitor, nintedanib, versus sorafenib in previously untreated patients with advanced hepatocellular carcinoma (HCC). 
Abstract:
Background: While sorafenib is established as the standard first-line treatment forpatients with advanced HCC, its use can be complicated by the occurrenceof drug-related adverse events (AEs). Nintedanib, a potent, oral tripleangiokinase inhibitor that targets VEGF, PDGF and FGF signaling (as wellas Flt3 and RET), has demonstrated clinical activity in various advancedsolid tumors with a relatively low incidence of AEs typically associatedwith angiogenesis inhibitors (e.g. skin toxicity, hypertension,hemorrhage, and hematologic toxicity) and is currently in phase III fornon-small cell lung cancer and ovarian cancer. In the Phase I,dose-finding stage of this ongoing, multicenter, open-label Phase I/IItrial (NCT01004003), 200mg twice daily (bid) was established as themaximum tolerated dose of nintedanib in previously untreated patientswith advanced HCC (Palmer D, et al. Ann Oncol 2012;23(Suppl 9):ix245[Abs740P]). Nintedanib had an acceptable liver AE profile; the most commonAEs were mild/moderate gastrointestinal toxicities.
Methods: The randomized Phase II stage of the trial aims to assess the efficacy, safety, and pharmacokinetics of nintedanib in comparison with sorafenib. Eligible patients have pathologically confirmed, measurable HCC that is not amenable to local therapy, ECOG Performance Status of ≤2, Child-Pugh score of 5–6 (Class A), AST/ALT levels ≤2× upper limit of normal, and no prior systemic therapy. Patients are being stratified by macrovascular invasion and/or extrahepatic spread and then randomized 2:1 to receive nintedanib 200mg bid or sorafenib 400mg bid in continuous 28-day cycles until progression or unacceptable toxicity. Overall, 93 patients were randomized between Sept 2011 and Nov 2012. The primary endpoint is time to progression (TTP) by independent review, according to RECIST 1.0. TTP will be estimated in the treated set by Kaplan–Meier methodology with treatment effects compared using a Cox proportional hazards model. Secondary endpoints include overall survival, tumor response, progression-free survival, safety and pharmacokinetics. Results are due late 2013.