Background: For biliary tract cancer (BTC), the addition of immunotherapy (durvalumab or pembrolizumab) to gemcitabine and cisplatin (GemCis) significantly improved overall survival (OS) in phase 3 clinical trials (RCTs). However, the interpretation and magnitude of the treatment effect is challenging because OS Kaplan–Meier curves violate the proportional hazards (PH) assumption. Analysis using restricted mean survival time (RMST) allows quantification of the benefits in the absence of PH. This systematic review and meta-analysis aims to assess the benefit of immunotherapy-based regimens for OS at 24 months using RMST analysis. Methods: A systematic review was conducted using studies published up to 8 November 2023. Only phase 3 RCTs evaluating the use of anti-PD-1/PD-L1 combined with GemCis and reporting OS were included. KM curves for OS were digitized, and the data were reconstructed. A meta-analysis for OS by RMST at 24 months was performed. Results: A total of 1754 participants from the TOPAZ-1 and KEYNOTE-966 trials were included. In TOPAZ-1, RMSTs at 24 months were 13.52 (7.92) and 12.21 (7.22) months with GemCis plus durvalumab and GemCis alone, respectively. In KEYNOTE-966, RMSTs at 24 months were 13.60 (7.76) and 12.45 (7.73) months with GemCis plus pembrolizumab and GemCis alone, respectively. Immunotherapy-based regimens showed a mean OS difference at 24 months by an RMST of 1.21 months [(95% CI: 0.49–1.93),p< 0.001, I2= 0%]. Conclusions: Immunotherapy-based regimens improve OS in advanced BTC. Given this magnitude of benefit, it is essential to weigh up individual patient factors, preferences, and potential risks. RMST analysis provides valuable information to patients and physicians, facilitating decision-making in a value-based medical environment.
背景：针对胆道癌（BTC），在吉西他滨联合顺铂（GemCis）方案基础上加用免疫治疗（度伐利尤单抗或帕博利珠单抗）在3期临床试验（RCTs）中显著改善了患者的总生存期（OS）。然而，由于OS的Kaplan-Meier曲线违反了比例风险（PH）假设，治疗效果的解读及其程度评估存在挑战。采用限制性平均生存时间（RMST）进行分析可在不满足PH假设的情况下量化治疗获益。本系统综述与荟萃分析旨在通过RMST分析评估基于免疫治疗的方案在24个月时对OS的获益情况。 方法：系统检索截至2023年11月8日发表的研究。仅纳入评估抗PD-1/PD-L1药物联合GemCis方案并报告OS的3期RCTs。对OS的KM曲线进行数字化处理并重建数据，采用RMST方法对24个月时的OS进行荟萃分析。 结果：共纳入来自TOPAZ-1和KEYNOTE-966试验的1754名受试者。在TOPAZ-1试验中，GemCis联合度伐利尤单抗组与单用GemCis组在24个月时的RMST分别为13.52（7.92）个月和12.21（7.22）个月。在KEYNOTE-966试验中，GemCis联合帕博利珠单抗组与单用GemCis组在24个月时的RMST分别为13.60（7.76）个月和12.45（7.73）个月。基于免疫治疗的方案在24个月时通过RMST计算的平均OS差异为1.21个月[（95% CI: 0.49–1.93），p<0.001，I²=0%]。 结论：基于免疫治疗的方案可改善晚期BTC患者的OS。鉴于该获益程度，必须权衡患者的个体因素、治疗偏好及潜在风险。RMST分析为患者和临床医生提供了有价值的信息，有助于在基于价值的医疗环境中进行临床决策。
肿瘤(癌症)患者之家