Wang Jiashou, Xu Yun, Hong Bo, Hou Qingjian, Chen Wenying, Zhang Wenxiong, Zheng Wen
Department of Interventional Diagnosis and Treatment, Shangrao People's Hospital, Shangrao, 334000, China.
Department of Oncology, Shangrao People's Hospital, No. 86 Shuyuan Road, Xinzhou District, Shangrao, 334000, China.
World J Surg Oncol. 2025 Jun 10;23(1):228. doi: 10.1186/s12957-025-03877-0.
The efficacy of PD-1/PD-L1 inhibitors plus chemotherapy (PIC) as a first-line treatment for advanced biliary tract cancer (BTC) remains controversial, given inconsistent findings regarding survival benefits and safety concerns. This meta-analysis systematically evaluates the safety and efficacy of PIC versus chemotherapy alone, aiming to provide more definitive guidance for BTC treatment decisions.
To identify phase 3 randomized controlled trials (RCTs) comparing PIC with chemotherapy alone in patients with advanced BTC, a comprehensive literature search was conducted across six databases. Primary outcomes were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included response rates and adverse events (AEs).
Two phase 3 RCTs (KEYNOTE-966 and TOPAZ-1) involving 1,754 patients met the inclusion criteria. Findings demonstrated that the PIC group had significantly improved OS (hazard ratio [HR]: 0.76 [0.66, 0.87]) and PFS (HR: 0.76 [0.66, 0.87]). The mOS (MD: 1.70 [1.51, 1.90] months) and mPFS (MD: 1.20 [0.61, 1.79] months) were also higher in the PIC group. OS and PFS advantages for the PIC group were confirmed across most subgroups. In the first two years of treatment, survival rates (OS and PFS) and extended duration of response in the PIC group increased over time. Both groups showed comparable total AEs, treatment-related AEs, ORR, and DCR. However, the PIC group had significantly higher rates of immune-related AEs (irAEs) and grade 3-5 irAEs.
PIC is associated with improved OS and PFS in advanced BTC compared to chemotherapy alone, though the elevated risk of irAEs calls for careful monitoring.
PROSPERO ID: CRD42024611835. PROSPERO link: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024611835 .
鉴于在生存获益和安全性方面的研究结果不一致，PD-1/PD-L1抑制剂联合化疗（PIC）作为晚期胆管癌（BTC）一线治疗的疗效仍存在争议。本荟萃分析系统评价了PIC与单纯化疗相比的安全性和疗效，旨在为BTC治疗决策提供更明确的指导。
为了确定比较PIC与单纯化疗治疗晚期BTC患者的3期随机对照试验（RCT），对六个数据库进行了全面的文献检索。主要结局为总生存期（OS）和无进展生存期（PFS），次要结局包括缓解率和不良事件（AE）。
两项涉及1754例患者的3期RCT（KEYNOTE-966和TOPAZ-1）符合纳入标准。结果表明，PIC组的OS（风险比[HR]：0.76[0.66，0.87]）和PFS（HR：0.76[0.66，0.87]）显著改善。PIC组的中位OS（MD：1.70[1.51，1.90]个月）和中位PFS（MD：1.20[0.61，1.79]个月）也更高。PIC组的OS和PFS优势在大多数亚组中得到证实。在治疗的前两年，PIC组的生存率（OS和PFS）和缓解持续时间随时间增加。两组的总AE、治疗相关AE、客观缓解率（ORR）和疾病控制率（DCR）相当。然而，PIC组的免疫相关AE（irAE）和3-5级irAE发生率显著更高。
与单纯化疗相比，PIC可改善晚期BTC的OS和PFS，尽管irAE风险升高需要仔细监测。
PROSPERO注册号：CRD42024611835。PROSPERO链接：https://www.crd.york.ac.uk/PROSPERO/view/CRD42024611835 。
