Evolving Paradigms in the Systemic Treatment of Advanced Gallbladder Cancer: Updates in Year 2022

Abstract

Gallbladder cancer (GBC) is a biological, anatomical, and clinically distinct subset of biliary tract cancers (BTC), which also include extra- and intra-hepatic cholangiocarcinoma. The advent of next-generation sequencing (NGS) clearly shows that GBC is genetically different from cholangiocarcinoma. Although GBC is a relatively rare cancer, it is highly aggressive and carries a grave prognosis. To date, complete surgical resection remains the only path for cure but is limited to patients with early-stage disease. The majority of the patients are diagnosed at an advanced, inoperable stage when systemic treatment is administered as an attempt to enable surgery or for palliation. Gemcitabine and platinum-based chemotherapies have been the main treatment modality for unresectable, locally advanced, and metastatic gallbladder cancer. However, over the past decade, the treatment paradigm has evolved. These include the introduction of newer chemotherapeutic strategies after progression on frontline chemotherapy, incorporation of targeted therapeutics towards driver mutations of genes including HER2, FGFR, BRAF, as well as approaches to unleash host anti-tumor immunity using immune checkpoint inhibitors. Notably, due to the rarity of BTC in general, most clinical trials included both GBC and cholangiocarcinomas. Here, we provide a review on the pathogenesis of GBC, past and current systemic treatment options focusing specifically on GBC, clinical trials tailored towards its genetic mutations, and emerging treatment strategies based on promising recent clinical studies.

Atlas of PD-L1 for Pathologists: Indications, Scores, Diagnostic Platforms and Reporting Systems

“…In this context, it had to be clarified that a real predictive role for this biomarker has been acknowledged for tumors of the esophagus, esophago–gastric junction and stomach [ 30 ]. Conversely, for intestinal cancers and for tumors of the pancreatobiliary system, PD-L1 has no recognized role in predicting the response to immunotherapy [ 30 , 31 , 32 , 33 , 34 ].…”

Therapeutic response analysis for patients with adenosquamous carcinoma of the gallbladder: data analysis based on the Surveillance, Epidemiology, and End Results (SEER) database

“…As the basis of biliary cancer treatment, adjuvant systemic therapy has been problematic for patients with GBC due to a dearth of clinical trials focused on this disease, with this being worse in GBASC for its even lower incidence (2,22,23). Akce et al (14) established a connection between increased survival with receipt of adjuvant systemic therapy in patients with GBASC.…”

Phosphorylated Proteins from Serum: A Promising Potential Diagnostic Biomarker of Cancer

“…In 2022, an estimated 12,130 GBC and other biliary cancers are expected to be diagnosed, with an estimated 4400 patients dying from these diseases. Prognosis is particularly poor in elderly and racial minorities [ 24 ]. Tan et al identified 24 differentially expressed proteins, which includes 12 upregulated and 12 downregulated proteins between gallbladder cancer patients and healthy controls [ 25 ].…”