Immunotherapy in Cholangiocarcinoma

Mechanism of Action and Clinical Efficacy

Immunotherapy works by blocking immune checkpoint proteins (PD-1/PD-L1) to restore the immune system's ability to recognize and destroy cancer cells, with pembrolizumab and durvalumab demonstrating significant clinical benefit particularly in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, as recommended by the American Association for the Study of Liver Diseases 1, 2
The European Society for Medical Oncology suggests that pembrolizumab achieves an objective response rate of 40.9% with complete responses in 21% of MSI-H/dMMR cholangiocarcinoma patients who progressed after first-line chemotherapy, with median progression-free survival of 4.2 months and median overall survival of 24.3 months, based on strong evidence 2, 3

The National Comprehensive Cancer Network recommends that immune checkpoint blockade should be considered a therapeutic option for patients with intrahepatic cholangiocarcinoma and dMMR/MSI-H who have progressed on first-line chemotherapy and have not received durvalumab in first-line, with a strength of evidence of high 1, 2
The American Society of Clinical Oncology suggests that gemcitabine plus cisplatin combined with durvalumab or pembrolizumab represents the standard of care for first-line treatment of unresectable or metastatic cholangiocarcinoma, achieving a hazard ratio of 0.76 (95% CI 0.64-0.91) and median overall survival of 12.9 months, based on moderate evidence 5

The European Society for Medical Oncology recommends that quality of life should be the primary focus with survival as a secondary endpoint, as achieving stable disease correlates with improved length and quality of life, with pembrolizumab demonstrating a favorable safety profile compared to chemotherapy 4, 7