ASCO GI Highlights

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.

Biliary tract cancers represent a heterogeneous group of tumors that includes intrahepatic cholangiocarcinoma (CCA), extrahepatic CCA, and gallbladder carcinoma. Teresa Macarulla, MD, PhD, Hospital Universitario Vall d’Hebron, Barcelona, Spain, and colleagues conducted a study to characterize the epidemiology of patients with biliary tract cancer, including patient management and survival outcomes. Dr Macarulla presented the results at the 2022 ASCO GI Cancers Symposium.

Data related to health-related quality of life (QOL), including financial toxicity, for patients with cholangiocarcinoma (CCA) who are receiving targeted therapies are limited. Jessica M. Keilson, MD, Winship Cancer Institute, Emory University, Atlanta, GA, and colleagues, in association with the Cholangiocarcinoma Foundation (CCF), conducted a patient-reported health-­related QOL study to gain insight into the effect of physical, psychosocial, and financial challenges on patients with CCA. Dr Keilson presented the results at the 2022 ASCO GI Cancers Symposium.

The global, double-blind, placebo-controlled, phase 3 TOPAZ-1 clinical trial evaluated the first-line chemoimmunotherapy regimen of the PD-L1 inhibitor durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer. Do-Youn Oh, MD, PhD, Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, South Korea, presented the results of the planned interim analysis for this study at the 2022 ASCO GI Cancers Symposium.

Derazantinib is a potent oral inhibitor of FGFR1, FGFR2, and FGFR3 that is being investigated in the phase 2 FIDES-01 clinical trial of patients with advanced intrahepatic cholangiocarcinoma (CCA) harboring FGFR2 fusions or rearrangements.

The subtypes of cholangiocarcinoma (CCA), including intrahepatic CCA and extrahepatic CCA, have various underlying tumor microenvironments, pathobiology, epidemiologic features, and risk factors; however, the genetic underpinnings of the CCA subtypes have not been previously defined.

Mutations associated with homologous recombination deficiency (HRD) have been identified in up to 25% of patients with biliary tract cancers; however, the proportion of patients with germline versus somatic mutations has not been previously defined.