Ahn Joseph C, Ng Wee Han, Yeo Yee Hui, Kim Hyun-Seok, Wang Yun, Trivedi Hirsh, Ayoub Walid S, Kuo Alexander, Rich Nicole, Parikh Neehar D, Abou-Alfa Ghassan K, Ma Kevin Sheng-Kai, Singal Amit G, Yang Ju Dong
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
University of Bristol Medical School, Bristol, UK.
Hepatology. 2025 Mar 28. doi: 10.1097/HEP.0000000000001328.
Immunotherapy has emerged as an effective treatment for advanced HCC. We aimed to investigate the real-world effectiveness of immunotherapy compared to lenvatinib in HCC.
From the TriNetX database, we used a target trial emulation framework and identified patients with HCC who received first-line treatment with immunotherapy (atezolizumab/bevacizumab or tremelimumab/durvalumab) or lenvatinib between or between August 2018 and December 2023. OS was compared using Kaplan-Meier analysis and Cox proportional hazards regression. After propensity score matching, 1203 patients were included in each group. Immunotherapy was associated with improved OS versus lenvatinib (median survival: 545 vs. 425 d; HR: 0.86, 95% CI: 0.76-0.97). Regarding treatment type, atezolizumab plus bevacizumab showed improved survival compared to lenvatinib (n=1070 in each group; HR: 0.87, 95% CI: 0.77-0.99), while the point estimate favored durvalumab plus tremelimumab versus lenvatinib (HR: 0.81, 95% CI: 0.59-1.12), though this difference was not statistically significant, likely due to small sample size. Regarding etiology, immunotherapy had improved OS compared to lenvatinib in viral hepatitis (n=510 in each group; HR: 0.74, 95% CI: 0.61-0.89) and alcohol-associated liver disease (n=190 in each group; HR: 0.65, 95% CI: 0.49-0.87), but not in metabolic dysfunction-associated steatotic liver diseases (n=156 in each group; HR: 0.96, 95% CI: 0.70-1.31).
In this real-world analysis, immunotherapy was associated with improved OS compared to lenvatinib in advanced HCC, with consistent benefit across most subgroups. These findings support the use of immunotherapy as a first-line treatment for advanced HCC.
免疫疗法已成为晚期肝癌的有效治疗方法。我们旨在研究免疫疗法与乐伐替尼相比在肝癌治疗中的真实疗效。
从TriNetX数据库中，我们采用目标试验模拟框架，确定了在2018年8月至2023年12月期间接受免疫疗法（阿替利珠单抗/贝伐珠单抗或曲美木单抗/度伐利尤单抗）或乐伐替尼一线治疗的肝癌患者。使用Kaplan-Meier分析和Cox比例风险回归比较总生存期。倾向评分匹配后，每组纳入1203例患者。与乐伐替尼相比，免疫疗法可改善总生存期（中位生存期：545天对425天；风险比：0.86，95%置信区间：0.76 - 0.97）。关于治疗类型，阿替利珠单抗加贝伐珠单抗与乐伐替尼相比生存期有所改善（每组n = 1070；风险比：0.87，95%置信区间：0.77 - 0.99），而度伐利尤单抗加曲美木单抗与乐伐替尼相比的点估计值更有利（风险比：0.81，95%置信区间：0.59 - 1.12），但这种差异无统计学意义，可能是由于样本量小。关于病因，在病毒性肝炎（每组n = 510；风险比：0.74，95%置信区间：0.61 - 0.89）和酒精性肝病（每组n = 190；风险比：0.65，95%置信区间：0.49 - 0.87）中，免疫疗法与乐伐替尼相比可改善总生存期，但在代谢功能障碍相关脂肪性肝病中（每组n = 156；风险比：0.96，95%置信区间：0.70 - 1.31）则不然。
在这项真实世界分析中，与乐伐替尼相比，免疫疗法在晚期肝癌中与总生存期改善相关，在大多数亚组中均有一致的获益。这些发现支持将免疫疗法作为晚期肝癌的一线治疗方法。
