Background In patients with advanced hepatocellular carcinoma (HCC) progressing after atezolizumab and bevacizumab, the optimal therapeutic sequence is still unclear and no second-line agent has proven its efficacy. Objectives The aim of this retrospective multicenter real-world cohort study was to provide an evaluation of the efficacy and safety of the use of second-line tyrosine kinase inhibitors (TKIs) in this population. Methods All patients with advanced HCC, treated in first-line setting by atezolizumab-bevacizumab, and who received at least one dose of treatment with TKI were included in this study. All the data were retrospectively collected from medical records. The primary outcome was progression-free survival (PFS). Secondary outcomes were overall survival (OS), overall global survival (OGS), and safety. A total of 82 patients were included in this study. Results Patients were assigned to the regorafenib group (n = 29, 35.4%) or other TKI (sorafenib n = 41, lenvatinib n = 8, or cabozantinib n = 4) group (n = 53). PFS was not significantly different between the two groups [2.6 versus 2.8 months, HR 1.07 (95% CI: 0.61-1.86), p = 0.818]. Median PFS rates were 2.6, 4.4, and 2.8 months in sorafenib-, lenvatinib-, and cabozantinib group, respectively. OS was statistically different between the regorafenib group and other TKI group [15.8 versus 7.0 months, HR 0.40 (95% CI: 0.20-0.79), p = 0.023]. When adjusting on confounding factors, there was still a difference in OS favoring the regorafenib group (adjusted hazard ratio 0.35, p = 0.019). OGS of patients who received regorafenib was improved compared to other TKI [18.6 versus 15.0 months, HR 0.42 (95% CI: 0.22-0.84), p = 0.036]. Twenty percent of patients had grade 3 and none had grade 4 or 5 adverse events. In patients who experienced disease progression and fit for a third-line treatment, 80% and 50% received cabozantinib in regorafenib group and other TKI group, respectively. Conclusion Efficacy of any TKI in the second-line setting was not affected by atezolizumab-bevacizumab treatment as first-line therapy. The safety profile in the second-line setting was consistent with the results shown in pivotal studies. PFS rates of patients were similar, regardless of TKI type. Regorafenib was associated with better OS and OGS rates compared to other TKI. These data need to be confirmed in prospective comparative studies.

中文翻译：

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除了阿特朱单抗加贝伐单抗治疗晚期肝细胞癌患者：酪氨酸激酶抑制剂在现实世界中的总体疗效和安全性。

背景 对于在阿特珠单抗和贝伐珠单抗治疗后进展的晚期肝细胞癌 (HCC) 患者，最佳治疗顺序仍不清楚，并且没有二线药物证明其疗效。目的 这项回顾性多中心现实世界队列研究的目的是评估二线酪氨酸激酶抑制剂 (TKI) 在该人群中使用的有效性和安全性。方法 本研究纳入所有在一线接受阿替利珠单抗-贝伐珠单抗治疗且接受至少一剂 TKI 治疗的晚期 HCC 患者。所有数据均从病历中回顾性收集。主要结局是无进展生存期（PFS）。次要结局是总生存期（OS）、总生存期（OGS）和安全性。本研究共纳入 82 名患者。结果患者被分配至瑞戈非尼组（n = 29，35.4%）或其他 TKI（索拉非尼 n = 41、乐伐替尼 n = 8 或卡博替尼 n = 4）组（n = 53）。两组之间的 PFS 无显着差异 [2.6 个月与 2.8 个月，HR 1.07 (95% CI: 0.61-1.86)，p = 0.818]。索拉非尼、乐伐替尼和卡博替尼组的中位 PFS 率分别为 2.6、4.4 和 2.8 个月。瑞戈非尼组和其他 TKI 组之间的 OS 存在统计学差异 [15.8 个月与 7.0 个月，HR 0.40 (95% CI: 0.20-0.79)，p = 0.023]。调整混杂因素后，总生存期仍存在有利于瑞戈非尼组的差异（调整后的风险比为 0.35，p = 0.019）。与其他 TKI 治疗相比，接受瑞戈非尼治疗的患者 OGS 有所改善 [18.6 个月与 15.0 个月，HR 0.42 (95% CI: 0.22-0.84)，p = 0.036]。20% 的患者出现 3 级不良事件，没有人出现 4 级或 5 级不良事件。在经历疾病进展且适合三线治疗的患者中，瑞戈非尼组和其他 TKI 组中分别有 80% 和 50% 的患者接受卡博替尼治疗。结论 作为一线治疗，任何 TKI 在二线治疗中的疗效均不受阿特珠单抗-贝伐珠单抗治疗的影响。二线治疗的安全性与关键研究中显示的结果一致。无论 TKI 类型如何，患者的 PFS 率相似。与其他 TKI 相比，瑞戈非尼具有更好的 OS 和 OGS 率。这些数据需要在前瞻性比较研究中得到证实。