Today sorafenib is approved as first-line therapy in patients with advanced, unresectable HCC, largely as a result of a landmark trial led by Dr. Llovet (N. Engl. J. Med. 2008;359:378–90). Now underway are half a dozen phase III clinical trials comparing sorafenib to a clutch of potential alternative first-line agents, including sunitinib (Sutent), brivanib, the multitargeted tyrosine kinase inhibitor linifanib, sorafenib plus doxorubicin, and sorafenib plus erlotinib (Tarceva).
“There is a blossoming of studies in phase III for advanced HCC. And since we have first-line therapy, now there is a need for second-line therapies for those patients who fail on sorafenib to have some hope. Two phase III second-line trials are underway: brivanib vs. placebo and everolimus (Afinitor) vs. placebo,” he noted.
Although Dr. Llovet is principal investigator in three of the phase III HCC trials, he confessed that he has been unable to persuade the sponsoring pharmaceutical companies to engage in what he calls “trial enrichment”: genetic profiling to select the best candidates for a given therapy, in the way that breast cancers are tested for overexpression of HER2 to identify women who are eligible for trastuzumab (Herceptin).
“We are moving toward that in HCC. I think in a reasonable period of time we will see more trial enrichment,” Dr. Llovet predicted.
All of this drug development activity is most welcome. During 1990–2005, deaths from liver and bile duct cancer in the United States increased by 47%, far and away the largest increase for any type of cancer, he said.
'There is a blossoming of studies in phase III for advanced HCC.'
Source DR. LLOVET
This genetic signature study is a major step forward in understanding the mechanism of HCC.
Source DR. WEDEMEYER