Search: A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Sorafenib Plus Erlotinib in Patients with Hepatocellular Carcinoma (HCC)

New molecularly targeted therapies against advanced hepatocellular carcinoma: From molecular pathogenesis to clinical trials and future directions

“…In the phase III SEARCH trial, advanced HCC patients were randomized to sorafenib plus either erlotinib or placebo. 34 Inclusion criteria were a histological and cytological diagnosis of unresectable HCC and Child-Pugh liver function class A. Median OS was 9.5 months with sorafenib plus erlotinib and 8.5 months with sorafenib (HR, 0.92; 95% CI, 0.78-1.1; P = 0.2).…”

“…Other reasons include liver toxicity, flaws in trial design or marginal antitumoral efficacy of the agents. When dissecting the results of recent trials, [30][31][32][33][34] we can speculate that the main shortcomings for sunitinib are liver toxicity and issues with trial design. 30 Other shortcomings include lack of efficacy for erlotinib, 34 toxicity for linifanib 33 and lack of efficacy and issues with trial design for brivanib.…”

“…When dissecting the results of recent trials, [30][31][32][33][34] we can speculate that the main shortcomings for sunitinib are liver toxicity and issues with trial design. 30 Other shortcomings include lack of efficacy for erlotinib, 34 toxicity for linifanib 33 and lack of efficacy and issues with trial design for brivanib. 31,32 Hepatocellular carcinoma is a heterogeneous disease, both in regard to its clinical manifestations with underlying liver disease, and its complex pathogenesis involving aberrant signaling in several molecular pathways.…”

Expert Perspectives on Evidence-Based Treatment Planning for Patients with Hepatocellular Carcinoma

“…69 Trials of bevacizumab, 70 brivanib, 71 sunitinib, 72 linifanib, 73 and everolimus 74 did not meet their end points. Various regimens have not fared much better; for example, results from the sorafenib plus erlotinib 75 and bevacizumab plus erlotinib 76 trials were disappointing. Nonetheless, the number of novel targeted agents in late-stage trials is encouraging, and we are hopeful for new FDA approvals in the future.…”

Current strategies of precision medicine on advanced liver cancer

“…19,20 About 25 molecularly targeted drugs have been undergone phase III clinical trial in HCC patients from 2007 to 2015, but no clinically effective drug has been found to be superior to Sorafenib. [21][22][23][24][25][26][27] In 2017, a phase III clinical trial on Lenvatinib for patients with unresectable HCC was reported at the ASCO annual meeting. The study found that Lenvatinib was superior to Sorafenib in the treatment of advanced liver cancer (mOS: 13.6 months vs. 12.3 months) 18 but with no statistical difference.…”