Erlotinib Ineffective for Advanced Liver Cancer

David H. Ilson, MD, PhD

Overall survival was not improved by adding erlotinib to standard sorafenib therapy.

The only approved systemic agent to treat inoperable or metastatic hepatocellular carcinoma (HCC) is sorafenib, a multikinase inhibitor that achieves only modest disease control and survival. Erlotinib — an epidermal growth factor receptor tyrosine kinase inhibitor — has shown modest antitumor activity in phase II trials of patients with advanced HCC.

Investigators now report results of the SEARCH trial, an industry-sponsored, multicenter, randomized, double-blind, placebo-controlled, phase III trial comparing first-line sorafenib plus either erlotinib or placebo in 720 patients with advanced HCC. All patients had Childs Pugh A liver disease; 76% and 75%, respectively, were treated in Europe or North America; 61% and 60% had performance status 0; 34% and 37% had hepatitis B etiology; and 30% and 24% had hepatitis C etiology.

Overall survival (the primary endpoint) was similar with sorafenib plus either placebo or erlotinib or placebo (9.5 and 8.5 months, respectively), as was time to disease progression (3.2 and 4.0 months). Overall response trended higher with erlotinib (6.6% and 3.9%), but the disease control rate was significantly higher with placebo (52.5% vs. 43.9%; P=0.021). Median duration of sorafenib therapy was longer in the placebo arm (123 vs. 86 days). Rates of adverse events in the two treatment arms were similar.

Citation(s):

Zhu AX et al. SEARCH: A phase III, randomized, double blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma. J Clin Oncol 2014 Dec 29; [e-pub ahead of print].