Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, Kurashiki, Japan.
J Gastroenterol. 2024 Dec;59(12):1107-1118. doi: 10.1007/s00535-024-02150-7. Epub 2024 Sep 18.
Although atezolizumab plus bevacizumab (Atezo/Bev) therapy has been used as the preferred first-line treatment for advanced hepatocellular carcinoma (HCC), up to 26% of patients do not achieve disease control, suggesting alternative treatments might be more beneficial for such patients. We investigated key predictors for refractoriness to Atezo/Bev therapy, particularly in the first-line setting.
We retrospectively analyzed 302 patients with HCC who received Atezo/Bev therapy between October 2020 and September 2022 across nine hospitals in Japan. Refractoriness was defined as best overall response (BOR) of progressive disease or stable disease and a progression-free survival (PFS) of < 180 days (RECIST v1.1). Clinical benefit was defined as BOR of partial/complete response or stable disease with PFS of ≥ 180 days. Baseline characteristics and potential predictors, identified through literature review, were compared between these groups. Stratifications of overall survival (OS), and PFS were also assessed.
Refractoriness was observed in 126 (41.7%) patients, while 154 (51.0%) achieved clinical benefit. Due to a significant association between the treatment line and refractory rate, the subsequent analysis focused on the first-line cohort (n = 214; 72 [33.6%] patients showed refractoriness). Among 13 potential predictors, the CRP and AFP in immunotherapy (CRAFITY) score had the best predictive performance, with refractory rates of 24.6%, 44.6%, and 57.9% in CRAFITY-0, 1, and 2 patients, respectively (p < 0.001). OS and PFS were also well-stratified by this scoring system.
Approximately one-third of patients were refractory to first-line Atezo/Bev therapy. The CRAFITY score demonstrated superior performance in predicting refractoriness.
尽管阿替利珠单抗联合贝伐珠单抗（Atezo/Bev）治疗已被用作晚期肝细胞癌（HCC）的首选一线治疗方法，但多达 26%的患者无法控制疾病，这表明替代治疗可能对这类患者更有益。我们研究了对 Atezo/Bev 治疗产生耐药性的关键预测因素，特别是在一线治疗环境中。
我们回顾性分析了 2020 年 10 月至 2022 年 9 月期间在日本九家医院接受 Atezo/Bev 治疗的 302 例 HCC 患者。耐药性定义为最佳总体缓解（BOR）为疾病进展或稳定疾病以及无进展生存期（PFS）<180 天（RECIST v1.1）。临床获益定义为部分/完全缓解或稳定疾病的 BOR，PFS≥180 天。通过文献回顾确定了基线特征和潜在预测因素，并比较了两组之间的差异。还评估了总生存期（OS）和 PFS 的分层。
126 例（41.7%）患者出现耐药性，154 例（51.0%）患者获得临床获益。由于治疗线与耐药率之间存在显著关联，因此后续分析集中在一线队列（n=214；72[33.6%]例患者出现耐药性）。在 13 个潜在预测因素中，免疫治疗中的 C 反应蛋白和甲胎蛋白（CRAFITY）评分具有最佳的预测性能，CRAFITY-0、1 和 2 分患者的耐药率分别为 24.6%、44.6%和 57.9%（p<0.001）。该评分系统也能很好地分层 OS 和 PFS。
约三分之一的患者对一线 Atezo/Bev 治疗产生耐药性。CRAFITY 评分在预测耐药性方面表现出色。
