Hepatic and pancreatobiliary cancers often present at advanced stages, and currently, there are very few approved therapeutic options. This chapter focuses on the predictive biomarkers for current therapies as well as selected alternative options that are currently being evaluated in Phase III trials for these malignancies. In a Phase III trial for advanced hepatocellular carcinoma (HCC), there was a significant improvement in overall survival for patients with elevated alpha-fetoprotein who received ramucirumab. A Phase II trial of glypican-3 (GPC3) peptide vaccines in HCC demonstrated lower recurrence rates in tumors that were GPC3-positive. Advanced HCC cases with high cellular mesenchymal-epithelial transcription factor (c-MET) expression have significantly improved overall survival on tivantinib. A study of adjuvant chemotherapy for pancreatic cancer reported improved survival in cases with low postoperative CA 19-9. High expression of human equilibrative nucleoside transporter 1 (hENT1) has been shown to predict significantly improved overall survival in both pancreatic cancer and cholangiocarcinoma after gemcitabine therapy. There are currently no predictive biomarker guidelines for hepatic, pancreatic, or biliary tumors. Additional clinical trials are required before consensus statements outlining the utility of biomarkers in the treatment of these cancers can be effectively formulated. Currently, there are many ongoing clinical trials designed to confirm and expand the roles of predictive biomarkers in hepatic and pancreatobiliary cancers. Incorporation of recent advances in molecular analysis and immunotherapy into clinical trials promises new hope for these dismal diagnoses.
Sasaki H, et al. Concurrent analysis of human equilibrative nucleoside transporter 1 and ribonucleotide reductase subunit 1 expression increases predictive value for prognosis in cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy. Br J Cancer. 2014;111(7):1275–84.CrossRefPubMedPubMedCentralGoogle Scholar
Llovet JM, et al. Plasma biomarkers as predictors of outcome in patients with advanced hepatocellular carcinoma. Clin Cancer Res. 2012;18(8):2290–300.CrossRefPubMedGoogle Scholar
Trojan J, Waidmann O. Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma. J Hepatocell Carcinoma. 2016;3:31–6.CrossRefPubMedPubMedCentralGoogle Scholar
Sawada Y, et al. Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients. Oncoimmunology. 2016;5(5):e1129483.CrossRefPubMedPubMedCentralGoogle Scholar
Pievsky D, Pyrsopoulos N. Profile of tivantinib and its potential in the treatment of hepatocellular carcinoma: the evidence to date. J Hepatocell Carcinoma. 2016;3:69–76.CrossRefPubMedPubMedCentralGoogle Scholar
Nordh S, Ansari D, Andersson R. hENT1 expression is predictive of gemcitabine outcome in pancreatic cancer: a systematic review. World J Gastroenterol. 2014;20(26):8482–90.CrossRefPubMedPubMedCentralGoogle Scholar
Sinn M, et al. Human equilibrative nucleoside transporter 1 expression analysed by the clone SP 120 rabbit antibody is not predictive in patients with pancreatic cancer treated with adjuvant gemcitabine – results from the CONKO-001 trial. Eur J Cancer. 2015;51(12):1546–54.CrossRefPubMedGoogle Scholar