Durvalumab: an investigational anti-PD-L1 antibody for the treatment of biliary tract cancer

ABSTRACT

Introduction: The prognosis of patients with advanced biliary tract cancer (BTC) remains dismal, with a 5-year overall survival rate of less than 10%. Although immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of several hematological and solid tumors, controversial results have been reported in BTC. In this setting, the anti-PD-L1 inhibitor durvalumab is currently under investigation in several clinical trials as monotherapy, or in combination with other pharmacological agents.

Areas covered: We offer an overview of immunotherapies for BTC, discuss recently published or presented data on durvalumab pharmacology, safety, and efficacy in the treatment of BTC and consider future research directions for the agent in this setting.

Expert opinion: The promising antitumor activity shown by durvalumab in early trials warrants further investigation because it may provide more effective, much needed treatment options. The results of clinical trials of this PD-L1 inhibitor, as a monotherapy or in combination, are eagerly awaited. Future efforts should focus on the identification and development of reliable biomarkers of response to durvalumab in BTC, clarifying the role of PD-L1 expression, microsatellite instability (MSI), mismatch repair (MMR), tumor mutational burden (TMB) and other emerging predictors.

KEYWORDS:

• Biliary tract cancer
• cholangiocarcinoma
• PD-L1
• immunotherapy
• immune-checkpoint inhibitors
• durvalumab
• MEDI4736

Article highlights

• Single-agent immunotherapy has been disappointing in advanced biliary tract cancer (BTC), with clinical trials reporting limited, or even no, benefit.

• PD-L1 inhibitor durvalumab is currently under investigation for advanced BTC; the promising antitumor activity shown in early trials on BTC warrants further investigation.

• The binding of durvalumab to PD-L1 results in a T-cell-mediated immune response against tumor cells.

• Clinical trials are evaluating durvalumab monotherapy, dual immune-checkpoint blockade, immunotherapy plus targeted therapies, immune checkpoint inhibitors (ICIs) plus systemic chemotherapy, and immunotherapy plus local ablative treatments.

• Future efforts pursue the identification and development of reliable biomarkers of response to durvalumab in BTC, clarifying the role of PD-L1 expression, microsatellite instability (MSI), mismatch repair (MMR), tumor mutational burden (TMB) and other emerging predictors.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.