Expert opinion on investigational drugs
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Expert Opin Investig Drugs · Apr 2021
ReviewTargeting FGFR in intrahepatic cholangiocarcinoma [iCCA]: leading the way for precision medicine in biliary tract cancer [BTC]?
Introduction: The increasing availability of next-generation DNA sequencing (NGS) opens the opportunity to tailor therapies to potential targets. Intrahepatic cholangiocarcinoma (iCCA) has the most actionable genomic targets of the hepatobiliary malignancies, including mutations in Isocitrate Dehydrogenase (IDH) and Fibroblast Growth Factor Receptor (FGFR), particularly FGFR2. With the recent accelerated approval of pemigatinib and several trials currently underway, FGFR2 inhibition will set the mold for tailored therapies in hepatobiliary cancer. ⋯ Expert opinion: While more mature data are needed from the trials in progress, currently published analyses show survival benefit with FGFR2 inhibitors in patients positive for FGFR2 fusion who have failed the standard of care. Infigratinib, futibatinib, pemigatinib and derazantinib have all demonstrated promising activity iCCA patients harboring FGFR2 fusion. Eventually, head-to-head trials will be needed to fully understand the benefits of each agent and the role of reversible versus irreversible FGFR2 inhibitors.
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Expert Opin Investig Drugs · Apr 2021
ReviewDurvalumab: an investigational anti-PD-L1 antibody for the treatment of biliary tract cancer.
Introduction: The prognosis of patients with advanced biliary tract cancer (BTC) remains dismal, with a 5-year overall survival rate of less than 10%. Although immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of several hematological and solid tumors, controversial results have been reported in BTC. In this setting, the anti-PD-L1 inhibitor durvalumab is currently under investigation in several clinical trials as monotherapy, or in combination with other pharmacological agents. ⋯ Expert opinion: The promising antitumor activity shown by durvalumab in early trials warrants further investigation because it may provide more effective, much needed treatment options. The results of clinical trials of this PD-L1 inhibitor, as a monotherapy or in combination, are eagerly awaited. Future efforts should focus on the identification and development of reliable biomarkers of response to durvalumab in BTC, clarifying the role of PD-L1 expression, microsatellite instability (MSI), mismatch repair (MMR), tumor mutational burden (TMB) and other emerging predictors.