Department of Surgery & CancerImperial College LondonHammersmith HospitalLondonUK.
Section of Gastroenterology, Hepatology and NutritionThe University of Chicago MedicineChicagoIllinoisUSA.
Hepatol Commun. 2022 Jul;6(7):1776-1785. doi: 10.1002/hep4.1927. Epub 2022 Apr 28.
The availability of immune checkpoint inhibitors (ICIs) for the management of advanced hepatocellular cancer (HCC) has changed the treatment paradigm. There are emerging questions regarding the efficacy of subsequent anticancer therapies. The primary aim of this retrospective, multicenter study was to examine the types of anticancer treatment received after ICIs and to assess the impact on post-ICI survival. We established an international consortium of 11 tertiary-care referral centers located in the USA (n = 249), Europe (n = 74), and Asia (n = 97), and described patterns of care following ICI therapy. The impact of subsequent therapy on overall survival (OS) was estimated using the Kaplan-Meier method and presented with a 95% confidence interval (CI). A total of 420 patients were treated with ICIs for advanced HCC after one line of systemic therapy (n = 371, 88.8%): 31 (8.8%) had died, 152 (36.2%) received best supportive care (BSC) following ICIs, and 163 patients (38.8%) received subsequent anticancer therapy. Tyrosine kinase inhibitors (TKIs, n = 132, 80.9%), in particular sorafenib (n = 49, 30.0%), were the most common post-ICI therapy followed by external beam radiotherapy (n = 28, 17.2%), further immunotherapy (n = 21, 12.9%), locoregional therapy (n = 23, 14.1%), chemotherapy (n = 9, 5.5%), and surgery (n = 6, 3.6%). Receipt of post-ICI therapy was associated with longer median OS compared with those who had received BSC (12.1 vs. 3.3 months; hazard ratio [HR]: 0.4 (95% CI: 2.7-5.0). No difference in OS was noted in those patients who received TKI before ICIs compared with those who received ICIs followed by TKI. Conclusion: Post-ICI therapy is associated with OS in excess of 12 months, suggesting a role for therapeutic sequencing. OS from TKI therapy was similar to that reported in registration studies, suggesting preserved efficacy following ICIs.
免疫检查点抑制剂 (ICI) 的出现改变了晚期肝细胞癌 (HCC) 的治疗模式。对于后续抗癌治疗的疗效存在一些新的问题。本回顾性、多中心研究的主要目的是研究 ICI 治疗后接受的抗癌治疗类型，并评估其对 ICI 后生存的影响。我们建立了一个由美国 (n=249)、欧洲 (n=74) 和亚洲 (n=97) 11 个三级转诊中心组成的国际联盟，并描述了 ICI 治疗后的治疗模式。使用 Kaplan-Meier 方法估计后续治疗对总生存期 (OS) 的影响，并以 95%置信区间 (CI) 表示。共有 420 例患者在一线系统治疗后接受 ICI 治疗晚期 HCC(n=371，88.8%)：31 例 (8.8%) 死亡，152 例 (36.2%) 在 ICI 后接受最佳支持治疗 (BSC)，163 例 (38.8%) 接受后续抗癌治疗。酪氨酸激酶抑制剂 (TKI，n=132，80.9%)，特别是索拉非尼 (n=49，30.0%)，是最常见的 ICI 后治疗方法，其次是外照射放疗 (n=28，17.2%)、进一步免疫治疗 (n=21，12.9%)、局部区域治疗 (n=23，14.1%)、化疗 (n=9，5.5%)和手术 (n=6，3.6%)。与接受 BSC 治疗的患者相比，接受 ICI 后治疗的患者中位 OS 更长(12.1 个月比 3.3 个月；风险比[HR]：0.4(95%CI：2.7-5.0)。ICI 前接受 TKI 治疗的患者与 ICI 后接受 TKI 治疗的患者的 OS 无差异。结论：ICI 后治疗与超过 12 个月的 OS 相关，提示治疗顺序的作用。TKI 治疗的 OS 与注册研究报告的相似，提示 ICI 后保留了疗效。
