A retrospective cohort study on the efficacy and safety for combination therapy of immunotherapy, targeted agent, and chemotherapy versus immunochemotherapy or chemotherapy alone in the first-line treatment of advanced biliary tract carcinoma

BACKGROUND: A paucity of effective treatment for biliary tract carcinoma (BTC) has necessitated the investigation into new therapies. As combinations of targeted therapy with immunotherapy are well-established in hepatocellular carcinoma, the GEMOX chemotherapy (gemcitabine and oxaliplatin) is the standard treatment for BTC. This study aimed to evaluate the efficacy and safety of immunotherapy in combination with targeted agent and chemotherapy in advanced BTC. METHODS: Patients who were pathologically identified advanced BTC and had received gemcitabine-based chemotherapy alone or in combination with anlotinib, and/or anti-programmed cell death protein-1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors such as camrelizumab as first-line treatment were retrospectively screened from The First Affiliated Hospital of Guangxi Medical University from February 2018 to August 2021. The outcomes included objective response rate (ORR), median overall survival (OS), and median progressive-free survival (PFS). Adverse events (AEs) were assessed according to the NCI-CTCAE v. 4.03. Patients were followed up weekly. RESULTS: A total of 35 patients were enrolled in this study: 11 patients treated with PD-1/PD-L1 inhibitor plus anlotinib and gemcitabine (arm A), 12 patients with the GEMOX combined with PD-1/PD-L1 inhibitor (arm B), and 12 patients with GEMOX (arm C). With a median follow-up time of 31.9 months (range, 23.8–39.7 months), the median OS was 16.8 months [95% confidence interval (CI): 7.0–not reached], 11.8 months (95% CI: 7.2–31.7 months), and 11.6 months (95% CI: 7.3–18.0 months) in arms A, B, and C, respectively (P=0.298). The median PFS was 16.8 months (95% CI: 7.0–NR), 6.0 months (95% CI: 5.1–8.7 months), and 6.3 months (95% CI: 4.6–7.0 months) in arms A, B, and C, respectively. The ORR were 63.6% in arm A, 33.3% in arm B, and 25.0% in arm C. AEs of all grades occurred in 33 (94.3%) patients. Grade 3–4 AEs in all patients included neutrophil count decrease (14.3%), aspartate aminotransferase increase (8.6%), alanine aminotransferase increase (8.6%), fatigue (5.7%), and blood bilirubin increase (5.7%). CONCLUSIONS: Anti-PD-1/PD-L1 immunotherapy in combination with anlotinib and gemcitabine showed promising efficacy and an acceptable safety profile for the BTC patients included in this study.