Durable Responses in Patients With Advanced Cholangiocarcinoma on Sequential Dual-agent Immunotherapy After Progressing on Single-agent Immunotherapy

Abstract

Objectives: Biliary tract tumors have a poor prognosis despite advancements in targeted therapies. More recent studies have started to investigate the use of combination immunotherapy in advanced biliary cancers. However, currently, there are no clinical trials investigating the use of dual-agent immunotherapy with ipilimumab and nivolumab as a sequential treatment after patients have progressed on single-agent immunotherapy. In this case series, we discussed 3 patients with advanced cholangiocarcinoma who have an objective response to dualagent immunotherapy with ipilimumab and nivolumab after having disease progression on pembrolizumab and multiple other failed lines of treatment.Materials and Methods: A case series, including 3 patients treated at the University of California, Irvine Chao Family Comprehensive Cancer Center, was completed.Results: Although none of the 3 patients had microsatellite instability or high tumor-mutation burden and were not necessarily predicted to have a response to dual-agent immunotherapy, all 3 patients had an objective radiographic and/or tumor-marker response to a combination of ipilimumab and nivolumab.Conclusions: This case series serves as proof of the concept that sequential immunotherapy can be beneficial after progression on singleagent immunotherapy for patients with advanced cholangiocarcinoma. This study can also serve as the foundation to build further tests on the true effectiveness and ideal duration of sequential therapy with dual immunotherapy agents.

Is there a role for combined anti–PD‐1/CTLA‐4 checkpoint blockade in the management of advanced biliary tract cancers?

“…Two other recent reports support the activity of ipilimumab/ nivolumab combination immunotherapy in patients with advanced biliary tract cancer who have progressed on chemotherapy and/or anti-PD-1 monotherapy and subsequently have obtained durable responses to combination immunotherapy. 5,6 In view of these findings, ipilimumab/nivolumab combination therapy may have a role in the treatment of advanced biliary tract cancers in later lines of therapy. Biomarker research will be crucial for better defining the patient population that derives a treatment benefit; the tumor mutation burden of the 39 patients with biliary tract cancer who were enrolled in CA209-538 was overall low and did not differ between responders and nonresponders, 7 whereas PD-L1 expression on tumor cells was enriched for response (O Klein MD, A Behren PhD May 2021).…”