Abstract
Brivanib, a selective dual inhibitor of fibroblast growth factor and VEGF signaling, has recently been shown to have activity as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). This phase II open-label study assessed brivanib as second-line therapy in patients with advanced HCC who had failed prior antiangiogenic treatment. Brivanib was administered orally at a dose of 800 mg once daily. The primary objectives were tumor response rate, time to response, duration of response, progression-free survival, overall survival (OS), disease control rate, time to progression (TTP), and safety and tolerability. Forty-six patients were treated. Best responses to treatment with brivanib (N = 46 patients) using modified World Health Organization criteria were partial responses for two patients (4.3%), stable disease for 19 patients (41.3%), and progressive disease for 19 patients (41.3%). The tumor response rate was 4.3%; the disease control rate was 45.7%. Median OS was 9.79 months. Median TTP as assessed by study investigators following second-line treatment with brivanib was 2.7 months. The most common adverse events were fatigue, decreased appetite, nausea, diarrhea, and hypertension. Brivanib had a manageable safety profile and is one of the first agents to show promising antitumor activity in advanced HCC patients treated with prior sorafenib.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide [1] and the third leading cause of cancer-related death [2]
Brivanib had a manageable safety profile and is one of the first agents to show promising antitumor activity in advanced hepatocellular carcinoma (HCC) patients treated with prior sorafenib
Several studies are evaluating novel combinations [9], and benefits have been observed with sorafenib, other single agents have not shown efficacy in HCC [10]
Summary
Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide [1] and the third leading cause of cancer-related death [2]. Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/). Agents that target the VEGF axis provide a survival benefit in patients with advanced-stage HCC [5, 6]. Current VEGF-targeted agents fail to produce enduring clinical responses in most patients as a result of de novo or acquired resistance [7, 8]. With regard to HCC, the only systemic agent that has been shown to improve survival is sorafenib, an oral multikinase inhibitor [5, 6]. Several studies are evaluating novel combinations [9], and benefits have been observed with sorafenib, other single agents (e.g., sunitinib) have not shown efficacy in HCC [10]
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