Hot Topics at ASCO-GI 2022

We have recently concluded the 4th Annual CCA Summit, which was held on October 13-15, 2022, in Denver, Colorado.

On September 2, 2022, the US Food and Drug Administration approved durvalumab in combination with gemcitabine/cisplatin for advanced biliary tract cancers (BTCs) on the basis of the TOPAZ-1 study.

A letter from the Editor-in-Chief, Milind M. Javle, MD.

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.