阿替利珠单抗联合贝伐单抗治疗伴有食管胃静脉曲张的不可切除肝细胞癌患者的疗效和安全性
Efficacy and safety of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma patients with esophageal-gastric varices.
作者信息
Tada Fujimasa, Hiraoka Atsushi, Tada Toshifumi, Hirooka Masashi, Kariyama Kazuya, Tani Joji, Atsukawa Masanori, Takaguchi Koichi, Itobayashi Ei, Fukunishi Shinya, Tsuji Kunihiko, Ishikawa Toru, Tajiri Kazuto, Ochi Hironori, Toyoda Hidenori, Ogawa Chikara, Nishimura Takashi, Hatanaka Takeshi, Kakizaki Satoru, Shimada Noritomo, Kawata Kazuhito, Naganuma Atsushi, Kosaka Hisashi, Matono Tomomitsu, Kuroda Hidekatsu, Yata Yutaka, Ohama Hideko, Nouso Kazuhiro, Morishita Asahiro, Tsutsui Akemi, Nagano Takuya, Itokawa Norio, Okubo Tomomi, Arai Taeang, Yokohama Keisuke, Nishikawa Hiroki, Imai Michitaka, Koizumi Yohei, Nakamura Shinichiro, Iijima Hiroko, Kaibori Masaki, Hiasa Yoichi, Kumada Takashi
机构信息
Gastroenterology Center, Ehime Prefectural Central Hospital, 83 Kasuga-cho, Matsuyama, Ehime, 790-0024, Japan.
Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan.
出版信息
J Gastroenterol. 2023 Nov;58(11):1134-1143. doi: 10.1007/s00535-023-02026-2. Epub 2023 Aug 1.
BACKGROUND
Bevacizumab inhibits vascular endothelial growth factor-A (VEGF-A), though is known to increase bleeding risk as an adverse event (AE). This study examined whether atezolizumab/bevacizumab (Atez/Bev) for unresectable hepatocellular carcinoma (uHCC) can be used for patients with esophageal-gastric varices (EGV).
METHODS
From October 2020 to December 2022, 506 uHCC patients (median 74 years) underwent an upper gastrointestinal endoscopy examination were enrolled, after exclusion of those with portal vein tumor thrombus (PVTT). Patients with EGV (≧ F1) were defined as EGV positive, and the cohort was divided into non-EGV (n = 355) and EGV (n = 151). Before introducing Atez/Bev, endoscopic treatment was performed, when necessary. Prognosis was evaluated, retrospectively.
RESULTS
The EGV group had significantly worse hepatic function, lower platelet count, elevated alpha-fetoprotein, and lower rate of extrahepatic metastasis, and lower rate of first-line use (each P < 0.05) than the other. However, progression-free survival (PFS) was also not a significantly difference between the EGV and non-EGV groups in analyses with (PFS rate at 6/12/18 months: 60%/38%/30% vs. 65%/46%/34%, P = 0.29) or without inverse probability weighting adjustment [median: 10.6 months (95% CI 8.3-14.0) vs. 10.5 months (95% CI 7.8-13.7), P = 0.79]. As for AEs, diarrhea was more frequent in the EGV group (≧ G3: 2.0% vs. 0.3%, P = 0.036), while no significant difference was noted for EGV hemorrhage (≧ G3: 1.3% vs. 0.6%, P = 0.345). Of 28 patients who underwent endoscopic treatments before introducing Atez/Bev, none showed EGV-associated hemorrhage.
CONCLUSIONS
Atez/Bev might be an effective therapeutic option in patients with EGV, when appropriate endoscopic treatment for EGV is performed.
背景
贝伐单抗可抑制血管内皮生长因子-A（VEGF-A），但已知其作为不良事件（AE）会增加出血风险。本研究探讨了阿替利珠单抗/贝伐单抗（Atez/Bev）用于不可切除肝细胞癌（uHCC）患者时，能否用于食管胃静脉曲张（EGV）患者。
方法
2020年10月至2022年12月，纳入506例接受上消化道内镜检查的uHCC患者（中位年龄74岁），排除门静脉肿瘤血栓（PVTT）患者。EGV（≧F1）患者被定义为EGV阳性，队列分为非EGV组（n = 355）和EGV组（n = 151）。在引入Atez/Bev之前，必要时进行内镜治疗。对预后进行回顾性评估。
结果
EGV组肝功能明显较差，血小板计数较低，甲胎蛋白升高，肝外转移率较低，一线使用率较低（各P < 0.05）。然而，在有（6/12/18个月无进展生存期[PFS]率：60%/38%/30% vs. 65%/46%/34%，P = 0.29）或无逆概率加权调整[中位值：10.6个月（95%CI 8.3 - 14.0）vs. 10.5个月（95%CI 7.8 - 13.7），P = 0.79]的分析中，EGV组和非EGV组之间的无进展生存期（PFS）也无显著差异。至于不良事件，腹泻在EGV组更常见（≧G3：2.0% vs. 0.3%，P = 0.036），而EGV出血无显著差异（≧G3：1.3% vs. 0.6%，P = 0.345）。在引入Atez/Bev之前接受内镜治疗的28例患者中，无一例出现EGV相关出血。
结论
当对EGV进行适当的内镜治疗时，Atez/Bev可能是EGV患者的一种有效治疗选择。
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