ASCO GI Highlights

The ongoing open-label, multicenter, phase 2a LUC2001 study is investigating the efficacy and safety of the FGFR inhibitor erdafitinib in a molecularly defined subset of Asian patients with advanced cholangiocarcinoma (CCA) harboring FGFR alterations whose disease progressed after ≥1 previous systemic therapies.

Given that monotherapy with immune checkpoint inhibitors, including the PD-1 inhibitor tislelizumab, has a modest effect in advanced biliary tract cancers, several combination strategies to improve the antitumor activity of immune checkpoint inhibitors are being explored.

The majority of patients with intrahepatic cholangiocarcinoma (CCA) present with advanced liver disease and are not candidates for curative resection. The current standard of care for patients with unresectable intrahepatic CCA is palliative chemotherapy with gemcitabine plus cisplatin.

Biliary tract cancers have dismal prognosis, and the treatment options are limited. Up to 15% of patients with biliary tract cancer have HER2-positive disease. Tucatinib is a highly selective HER2-­directed tyrosine kinase inhibitor.

Ivosidenib is a first-in-class inhibitor of IDH1 mutation that is indicated for the treatment of previously treated, locally advanced or metastatic cholangiocarcinoma (CCA) and IDH1 mutation. This indication was approved based on the results of the phase 3 ClarIDHy clinical trial, which demonstrated significant improvement in progression-free survival with ivosidenib compared with placebo in patients with previously treated, unresectable or metastatic CCA harboring IDH1 mutations.

Immune checkpoint inhibitors used as monotherapy have dem­onstrated only modest activity in unselected patients with advanced biliary tract cancers, highlighting the need for novel strategies to improve patient outcomes. Granulocyte macrophage colony-stimulating factors (GM-CSF) show immunomodulatory effects and may therefore potentiate the activity of immune checkpoint inhibitors.

The current standard of care for the first-line treatment of patients with advanced biliary tract cancer is chemotherapy combination of gemcitabine plus cisplatin; however, this regimen yields only modest responses, underscoring the need for novel, more active treatments. Human epidermal growth factor receptor (HER) tyrosine kinases are often overexpressed in patients with biliary tract cancers.

The multicenter, single-arm, phase 1b/2 BilT-03 study evaluated the benefit of a chemoimmunotherapy regimen that combines the 3-drug chemotherapy regimen of liposomal irinotecan, 5-fluorouracil (5-FU), and leucovorin, plus the PD-1 monoclonal antibody nivolumab, as second-line therapy in patients with advanced biliary tract cancers. The results were presented by Vaibhav Sahai, MBBS, MS, University of Michigan, Ann Arbor, at the 2022 ASCO GI Cancers Symposium.

Stereotactic body radiotherapy (SBRT) is increasingly being used for the treatment of patients with primary or metastatic liver cancer. A single-institution study was conducted to assess the incidence of central hepatobiliary adverse events (AEs) in patients with liver malignancies who were treated with SBRT, and to evaluate the relation with planned dosimetry to define predictors to minimize AEs. The results were presented by Nitika Thawani, Dignity Health Cancer Institute, Phoenix, AZ, at the 2022 ASCO GI Cancers Symposium.