Evaluating the Therapeutic Potential of Durvalumab in Adults with Locally Advanced or Metastatic Biliary Tract Cancer: Evidence to Date

Abstract

Advanced biliary tract cancers (BTCs) have historically been managed with chemotherapy but, in recent years, this treatment paradigm has begun to shift with the introduction of immune checkpoint inhibitors in addition to standard of care chemotherapy. The tumor microenvironment of BTC may be enriched with regulatory T lymphocytes and immune checkpoint expression in some patients. Durvalumab, an anti-programmed death ligand-1 (PD-L1) antibody, in combination with gemcitabine and cisplatin, has now received United States Food and Drug Administration approval for treatment of advanced BTC. Regulatory approval was based on the Phase III, randomized TOPAZ-1 trial that demonstrated survival benefit with addition of durvalumab to gemcitabine plus cisplatin compared to chemotherapy alone. The combination of chemotherapy and immunotherapy was well tolerated, and a subset of patients were able to achieve a durable response, with a 2-year overall survival rate of 23.6%. However, limitations remain in identifying which patients are most likely to benefit from immune checkpoint inhibition. Future study should aim to identify biomarkers predictive of substantial benefit, as well as the role of immune checkpoint inhibition in combination with targeted therapies and radiotherapy in the management of advanced BTC.

Keywords:

• durvalumab
• immunotherapy
• cholangiocarcinoma
• bile duct cancers

Abbreviations

BTC, biliary tract cancer; PD-L1, programmed death ligand-1; CCA, cholangiocarcinoma; GC, gallbladder carcinoma; AC, ampullary carcinoma; OS, overall survival; TME, tumor microenvironment; PD-1, programmed cell death protein 1; CTLA-4, cytotoxic T-lymphocyte associated protein 4; PFS, progression free survival; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year; MSI-H, high microsatellite instability; dMMR, deficient mismatch repair; TMB-H, high tumor mutation burden.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

Zhaohui Jin reports advisory board for Novartis, QED therapeutics, Lilly, GlaxoSmithKlein, Daiichi Sankyo/Astra Zeneca, Exelixis, and Elevar Therapeutics. Amit Mahipal reports speakers bureau, advisory board for AstraZeneca; speakers bureau for Exelixis; advisory board for Taiho Oncology and Elevar Therapeutics; and research funding from Pfizer. The authors report no other conflicts of interest in this work.

Additional information

Funding

There is no funding to report.