Analysis of the effectiveness and safety of targeted therapy combined with immune checkpoint inhibitors and systemic chemotherapy in the first-line treatment of advanced biliary malignancies
Authors: Zhao Lu , Zhang Zhengfeng , Wang Dazhen , Yang Liu , Liu Ze , Lou Changjie 
Published: December 2024

Background
The paucity of effective treatments for biliary tract carcinoma (BTC) necessitates the development of new therapies. Although targeted combination immunotherapy has demonstrated encouraging results in treating a range of solid tumors, more research is needed to determine the safety and efficacy of this treatment for patients with advanced BTC. Therefore, this study aimed to assess the efficacy and safety of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors combined with systemic chemotherapy and targeted therapy as first-line treatments in patients with advanced BTC.
Methods
We retrospectively analyzed 172 patients with advanced BTC who received systemic treatment at the Affiliated Tumor Hospital of Harbin Medical University Cancer Hospital between 2020 and 2023. Outcomes included objective response rate (ORR), median overall survival (OS), and median progression-free survival (PFS). Adverse events were assessed according to the NCICTCAE v. 4.03.
Results
A total of 172 individuals were enrolled and categorized into four groups: Group A received chemotherapy plus PD-1 antibody and lenvatinib; Group B received chemotherapy and PD-1 antibody and bevacizumab; Group C received chemotherapy and PD-1 antibody; and Group D received chemotherapy alone. The median OS was 13.63 months (95% confidence interval [CI]: 12.37–14.89), 12.41 months (95% CI: 10.67–12.32), 11.23 months (95% CI: 9.39–13.07), and 8.86 months (95% CI: 7.28–10.44) in groups A, B, C, and D, respectively (P = 0.312). In Groups A, B, C, and D, the median PFS was 12.42 months, 11.05 months, 8.89 months, and 6.02 months. A statistically significant difference was observed (t = 2, 95% CI:11.31–13.53, P < 0.01). The ORR was 45.00% (17/40) in Group A, 34.78% (16/46) in Group B, 16.67% (5/30) in Group C, and 17.86% (10/56) in Group D. The disease control rate was 87.50% (35/40), 8.26% (36/46), 76.67% (23/30), and 58.93% (33/56) in Groups A, B, C, and D, respectively. Regression analysis showed that patients' metastasis site, whether the neutrophil-lymphocyte ratio was < 2.3, and whether chemotherapy was administered through hepatic artery embolization were factors influencing median OS and PFS. Among the treatment-related adverse events (TRAEs), the grade 3–4 drug-related adverse event with the highest incidence was reactive skin of the hands and feet (12.8%, 22/172). The difference in TRAEs between levatinib and bevacizumab was not statistically significant, and their adverse effects were mainly gastrointestinal, including loss of appetite, nausea, vomiting, constipation, and diarrhea. The targeted therapy group had 20 cases (23.3%) of grade 3 adverse reactions, primarily including malaise in four cases (4.7%), skin reactions of the hands and feet in 10 cases (11.6%), loss of appetite in four cases (4.7%), and dizziness in two cases (2.3%).
Conclusion
In the first-line treatment of patients with advanced BTC, a targeted combination of PD-1/PD-L1 inhibitors and chemotherapy demonstrated improved antitumor efficacy and safety, making it a viable and manageable treatment option.