Posted: Tuesday, April 18, 2023
“Genomic profiling is the standard of care in the management of these cancers [hepatobiliary cancers], stated Mitesh J. Borad, MD, of the Mayo Clinic Comprehensive Cancer Center, Phoenix, at the NCCN 2023 Annual Conference. He discussed current therapeutic strategies for treating aggressive hepatocellular carcinoma and biliary tract cancers, along with the genomic landscapes of these patients.
Sorafenib has been the standard of care for patients with advanced or metastatic disease and has been tested in two pivotal trials: the phase III SHARP trial, and the Asia-Pacific trial. However, another first-line treatment option has become available; lenvatinib showed activity in hepatocellular carcinoma during a phase II study, a finding built upon the findings of the REFLECT study. “There was some numerical improvement with lenvatinib over sorafenib, but this was noninferior…. In the clinic, you could pick either one,” commented Dr. Borad. “In a subset of patients [with hepatocellular carcinoma], there is T-cell infiltration, particularly CD8-positive T cells, that you could leverage with immune checkpoint inhibitors.”
Cancers of the biliary tract, such as cholangiocarcinoma and gallbladder cancer, are the second-most common set of hepatobiliary cancers. Gemcitabine was established as the global standard of care for biliary tract cancer over a decade ago with the ABC-02 trial, the results of which favored a doublet regimen with cisplatin and later paved the way for the SWOG 1815 trial.
Currently, the incidence of gene fusions among patients with intrahepatic cholangiocarcinoma is around 10%, with known mutations including FGFR, IDH, and BRAF. Many newer inhibitors are currently under investigation, according to Dr. Borad, and futibatinib may be able to overcome many of the resistance mutations, particularly polyclonal mutations.
Disclosure: Dr. Borad reported no conflicts of interest.