Real-world survival outcomes of patients with cholangiocarcinoma receiving chemotherapy versus chemo-immunotherapy: A TriNetX database analysis.

Abstract

e16305 Background: Cholangiocarcinoma is an aggressive malignancy with poor prognosis, with median overall survival under 12 months in advanced disease. Following the TOPAZ-1 and KEYNOTE-966 trials, chemo-immunotherapy has become standard of care; however, real-world survival data across diverse populations are limited. We evaluated overall survival and safety outcomes of chemo-immunotherapy versus chemotherapy alone using a large international database. Methods: We performed a retrospective international cohort study using the TriNetX Global Collaborative Network. Adults with intrahepatic or extrahepatic cholangiocarcinoma treated between January 1, 2000, and December 31, 2024 were included, excluding those with prior malignancies or pre-index treatment. Chemo-immunotherapy (platinum-based chemotherapy plus durvalumab or pembrolizumab) was compared with chemotherapy alone. The primary outcome was overall survival at 6 months, 1 year, and 2 years; secondary outcomes included hospitalization, sepsis, hematologic toxicity, and immune-related adverse events. Kaplan–Meier and Cox proportional hazards analyses were performed after propensity score matching. Results: After propensity score matching, 1,362 patients were included per cohort with balanced baseline characteristics. At 1 year, chemo-immunotherapy improved overall survival (56.2% vs 50.4%; HR 0.84, 95% CI 0.74–0.94; p = 0.004), consistent with TOPAZ-1 and KEYNOTE-966. This benefit persisted at 2 years, with longer median overall survival (443 vs 370 days; HR 0.88, 95% CI 0.79–0.99; p = 0.019) and sustained Kaplan–Meier separation, though 2-year survival rates were similar. Hospitalization, sepsis, and palliative care rates were comparable however non-significant. Hematologic toxicity was modestly higher with chemo-immunotherapy, while immune-related adverse events remained infrequent, supporting an acceptable real-world safety profile. Conclusions: In this large real-world cohort, chemo-immunotherapy significantly improved 1- and 2-year overall survival versus chemotherapy, with manageable hematologic toxicity and low immune-related adverse events, supporting its use as first-line therapy and validating trial results in diverse patients. Clinical outcomes: chemo-immunotherapy vs chemotherapy alone. Outcome Time Point Chemo-Immunotherapy Chemotherapy Alone Effect Estimate Overall Survival (%) 6 months 73.78 69.97 HR 0.84 (CI 0.72–0.98) 1 year 56.2 50.4 HR 0.84 (0.74–0.94) 2 years 33 32.5 HR 0.88 (0.79–0.99) Hospitalization (Risk) 2 years 0.37 0.32 RR 0.83 (0.70–1.03) Sepsis 2 years 0.18 0.15 RR 1.15 (0.90–1.13) Palliative care 2 years 0.15 0.16 RR 0.91 (0.76–1.10) Hematologic toxicity 2 years 0.17 0.14 RR:1.17 (0.8-0.9) Pneumonitis 2 years 0.08 0.07 RR 1.15 (0.8-1.5) Colitis 2 years 0.06 0.05 RR 1.11 (0.8–1.5)