Kamya Sankar , Jun Gong , Arsen Osipov , Steven A. Miles , Kambiz Kosari, , Nicholas N. Nissen 、Andrew E. Hendifar , Ekaterina K. Koltsova , and Ju Dong Yang 西达-西奈医学中心塞缪尔-奥斯钦综合癌症研究所; 西达-西奈医学中心综合移植中心; 西达-西奈医学中心塞缪尔-奥斯钦综合癌症研究所。 西奈医疗中心; 雪松-西奈医疗中心斯密特心脏研究所; 胃肠病学和肝脏病学卡什分部、 美国加利福尼亚州洛杉矶雪松-西奈医疗中心
HIMALAYA试验对CTLA-4和PD-1联合阻断疗法进行了研究,该疗法于2022年再次获批用于一线治疗。在这项研究中,不可切除的治疗无效HCC患者被随机分配接受曲妥珠单抗300毫克(一剂)加杜瓦单抗1500毫克,每3周一次(STRIDE)、杜瓦单抗1500毫克,每4周一次或索拉非尼400毫克,每日两次。接受STRIDE治疗的患者中位OS更高(16.4个月 vs. 16.56个月 vs. 13.77个月;HR 单用durvalumab的OS不劣于索拉非尼(HR 0.86,非劣效边距1.08)。接受STRIDE治疗的患者中有50.5%发生了3-4级治疗相关不良事件,接受durvalumab治疗的患者中有37.1%发生了3-4级不良事件,接受索拉非尼治疗的患者中有 发生了3-4级不良事件。目前,durvalumab和tremelimumab联合疗法已被批准用于晚期HCC患者的一线治疗。对于不适合联合使用ICl或抗血管生成药物的患者,可考虑使用Durvalumab单药治疗。
在CheckMate 040(1/2期研究)中,晚期HCC患者按1:1随机分配:1的比例随机接受尼妥珠单抗1 加伊匹单抗 ,每3周一次,然后接受尼妥珠单抗维持治疗(A组);尼妥珠单抗3 加伊匹单抗 ,然后接受尼妥珠单抗维持治疗,每3周一次(B组);或尼妥珠单抗 ,每2周一次,加伊匹单抗 ,每6周一次(C组)。 组患者的客观反应率(A、B和C组分别为 vs. vs. )和中位OS(22.8 vs. 12.5 vs. 12.7个月)较高; 然而,这项研究的动力不足以检测治疗组之间的差异。治疗组A的3级或4级治疗相关不良事件发生率以及因毒性反应而停药的发生率确实较高。这种联合治疗方案(治疗组 A)随后获得了 FDA 的加速批准,用于治疗索拉非尼治疗进展后的 HCC 患者。这种联合疗法目前正被研究用于 HCC 患者的一线治疗(NCT04039607)。表 2 总结了评估 ICI 单药或联合疗法治疗 HCC 的主要试验。
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缩写:
HCC:肝细胞癌;NASH:非酒精性脂肪性肝炎;HBV:乙型肝炎病毒;HCV:丙型肝炎病毒;ICI:免疫检查点抑制剂;PD-L1:程序性死亡配体1;PD-1:程序性细胞死亡蛋白1;BCLC:巴塞罗那肝癌诊所;TACE,经动脉化疗栓塞;Y90,钇-90;TKI,酪氨酸激酶抑制剂;OS,总生存期;PFS,无进展生存期;CTLA-4,细胞毒性 T 淋巴细胞抗原-4;RT,放射治疗;TARE,经动脉放射栓塞;LEN,来伐替尼