Response to pembrolizumab after progression on durvalumab in cholangiocarcinoma: a case report of immune checkpoint inhibitor switching.

Currently, combination therapy incorporating immune checkpoint inhibitors (ICIs) is the standard first-line treatment for advanced biliary tract cancer (BTC). However, the relative efficacy of anti-PD-1 and -L1 antibodies remains unclear, and evidence regarding ICI switching after treatment failure is limited. Here, we report a case of advanced distal cholangiocarcinoma in which pembrolizumab demonstrated clinical efficacy after durvalumab failure, with partial response maintained for six months. Pembrolizumab treatment was discontinued because of interstitial pneumonitis requiring corticosteroid therapy. Immunohistochemical analysis demonstrated staining for PD-L1 and -L2 in the tumor cells. Anti-PD-1 antibodies inhibit interactions between PD-L1 and -L2, whereas anti-PD-L1 antibodies do not affect PD-L2. Although the mechanisms underlying the response remain unclear, blockade of the PD-L2-PD-1 axis may have contributed to the clinical response to pembrolizumab after durvalumab failure. This case suggests that switching from anti-PD-L1 to anti-PD-1 therapy may represent an individualized therapeutic option in selected patients with BTC.