Introduction: Patients with advanced hepatocellular carcinoma have a dismal prognosis; only a subset of patients with advanced HCC will benefit from treatment with immunotherapy. We searched for clinical characteristics predicting exceptional long-term survival in HCC patients treated with immune checkpoint inhibitors.
Methods: We compared clinical characteristics of 59 patients with advanced hepatocellular carcinoma treated with immunotherapy with and without locoregional therapy between 2013– 2019. We compared patients who lived less than 12 months with patients who lived more than 3 years. Traits of short-term (31 patients) and long-term (5 patients) survivors were compared. Patients who died between 12 months and 3 years of starting treatment on protocol were not included in the analysis.
Results: Two out of five patients (40%) in the long-term survival group had a partial response (PR) or a complete response (CR) per the modified Response Evaluation Criteria in Solid Tumors (mRECIST), while, of the 31 patients in the short-term survival group, only 2 (6.5%) had a CR or PR. Two of the 5 patients with a long-term survival had immune-related adverse events grade 3 or 4 (IrAEs-3/4). None of the patients in the short-term survival group had IrAEs-3/4. The patients, who presented with IrAEs-3/4, which included colitis and adrenal insufficiency, continued to have a response off treatment. The median overall survival (OS) was 11.8 months (95% CI: 7.8– 15.4 months), with a 12-month OS of 46.6% (95% CI: 33.4– 58.8%) and a 3-year OS of 12.5% (95% CI: 5.0– 23.7%).
Conclusion: We found a possible association between immune-related adverse events grade 3 and 4 and long-term survival in patients with advanced HCC. The cases in our analysis represent extraordinary defiance of the usual predicted dismal course of advanced HCC.

Keywords: hepatocellular carcinoma, immunotherapy, long-term overall survival, immune-related adverse events, tremelimumab, durvalumab

中文翻译：

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免疫检查点治疗晚期肝细胞癌长期生存的临床指标

简介：晚期肝细胞癌患者预后不佳；只有一部分晚期 HCC 患者会受益于免疫治疗。我们搜索了预测接受免疫检查点抑制剂治疗的 HCC 患者长期生存的临床特征。
方法：我们比较了 2013 年至 2019 年间 59 名接受免疫治疗和不接受局部区域治疗的晚期肝细胞癌患者的临床特征。我们比较了生存时间少于 12 个月的患者和生存时间超过 3 年的患者。比较了短期（31 名患者）和长期（5 名患者）幸存者的特征。分析中不包括在开始治疗后 12 个月至 3 年内死亡的患者。
结果：根据修改后的实体瘤反应评估标准 (mRECIST)，在长期生存组中，五分之二的患者 (40%) 获得了部分缓解 (PR) 或完全缓解 (CR)，而在 31在短期生存组中，只有 2 名（6.5%）患者达到 CR 或 PR。5 名长期存活患者中有 2 名出现 3 级或 4 级免疫相关不良事件 (IrAEs-3/4)。短期生存组患者均未出现 IrAEs-3/4。出现 IrAEs-3/4（包括结肠炎和肾上腺功能不全）的患者继续对治疗产生反应。中位总生存期（OS）为 11.8 个月（95% CI：7.8-15.4 个月），12 个月 OS 为 46.6%（95% CI：33.4-58.8%），3 年 OS 为 12.5%（ 95% CI：5.0– 23.7%）。
结论：我们发现 3 级和 4 级免疫相关不良事件与晚期 HCC 患者的长期生存之间可能存在关联。我们分析中的案例代表了对通常预测的晚期 HCC 惨淡病程的非凡挑战。

关键词：肝细胞癌，免疫治疗，长期总生存期，免疫相关不良事件，tremelimumab，durvalumab