First-line PD-1 inhibitors combination therapy for patients with advanced cholangiocarcinoma: A retrospective real-world study

Combination therapy with programmed cell death protein-1 (PD-1) inhibitors is currently the first-line treatment for advanced cholangiocarcinoma (CCA) in real-world settings. However, its effectiveness and safety are yet to be established. This study sought to assess the impact of this approach on the survival of this patient population. Our study included patients with advanced CCA who received first-line PD-1 inhibitors combination therapy at our hospital between September 2020 and April 2022 and were followed up until October 2022. Kaplan-Meier method was used to plot the survival curves. The Log-Rank method was used to compare differences in progression-free survival (PFS) and overall survival (OS) between groups. A total of 54 patients with advanced CCA were enrolled. The objective response rate (ORR) and disease control rate (DCR) were 16.7% and 79.6%, respectively. The median PFS and OS were 6.6 (95% CI: 3.9–9.3) months and 13.9 (95% CI: 10.0–17.8) months, respectively. 88.9% of patients (n = 48) experienced at least one adverse event (AE) with grade ≥ 3 AEs occurring in 20 patients (37.0%). The most common grade ≥ 3 AEs were neutropenia (n = 6, 11.1%), anemia (n = 6, 11.1%), and thrombocytopenia (n = 6, 11.1%). 28 patients (51.9%) developed at least one immune-related adverse event (irAE). The most common irAEs reported were rash (n = 12, 22.2%), hypothyroidism (n = 11, 20.4%), and pruritus (n = 5, 9.3%). Four patients (7.4%) developed grade ≥ 3 irAEs, including rash (n = 1, 1.9%), pruritus (n = 1, 1.9%), colitis (n = 1, 1.9%), and pancreatitis (n = 1, 1.9%). In addition, patients with CEA ≤ 5 ng/ml prior to PD-1 inhibitors combination therapy experienced longer median PFS (9.0 months vs. 4.5 months, P = 0.016) and median OS (17.5 months vs. 11.3 months, P = 0.014) than those with CEA > 5 ng/ml. Combination therapy with PD-1 inhibitors has demonstrated promising efficacy and manageable adverse events as a first-line treatment for advanced CCA in the real world.