分子靶向药物、免疫检查点抑制剂、肝动脉灌注化疗及其联合疗法在晚期肝细胞癌中的安全性和疗效比较：标志性试验进展的研究结果
Comparative safety and efficacy of molecular-targeted drugs, immune checkpoint inhibitors, hepatic arterial infusion chemotherapy and their combinations in advanced hepatocellular carcinoma: findings from advances in landmark trials.
作者信息
Pan Yangxun, Wang Ruojing, Hu Dandan, Xie Wa, Fu Yizhen, Hou Jiajie, Xu Li, Zhang Yaojun, Chen Minshan, Zhou Zhongguo
机构信息
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 510060 Guangzhou, Guangdong, China.
Department of Liver Surgery, Sun Yat-Sen University Cancer Center, 510060 Guangzhou, Guangdong, China.
出版信息
Front Biosci (Landmark Ed). 2021 Oct 30;26(10):873-881. doi: 10.52586/4994.
: Several recent phase 3 trials have reported manageable safety profiles and promising antitumor activities of molecular-targeted drugs (MTDs; sorafenib, lenvatinib), immune checkpoint inhibitors (ICIs; nivolumab, pembrolizumab, atezolizumab), hepatic arterial infusion chemotherapy (HAIC) and their combinations in advanced hepatocellular carcinoma (AHCC); however, head-to-head comparisons among these regimens are lacking. : We aimed to comprehensively review and compare the efficacy and safety of different MTDs, ICIs, HAIC and their combinations in AHCC. Adverse events (AEs), disease control rates (DCRs), objective response rates (ORRs), overall survival (OS) and progression-free survival (PFS) were assessed. : The pooled incidence rates of grade 1-5/3-5 AEs were 98.0%/48.6%, 98.3%/57.4%, 91.4%/22.0%, 96.4%/54.6%, 98.2%/61.1%, 86.3%/34.1%, 88.9%/9.4%, and 95.2%/53.2% for sorafenib, lenvatinib, nivolumab, pembrolizumab, atezolizumab plus bevacizumab, HAIC-cisplatin plus sorafenib, HAIC-oxaliplatin, and HAIC-oxaliplatin plus sorafenib, respectively, which suggested that nivolumab exhibited optimal safety regarding grade 1-5 AEs, whereas HAIC-oxaliplatin monotherapy ranked lowest regarding grade 3-5 AEs. According to RECIST1.1, lenvatinib (72.8%), atezolizumab plus bevacizumab (73.6%), HAIC-oxaliplatin (78.8%) and HAIC-oxaliplatin plus sorafenib (75.2%) showed higher DCRs than sorafenib (57.3%), nivolumab (33.9%), and pembrolizumab (62.3%), whereas only HAIC-oxaliplatin-based treatments demonstrated a higher ORR than the others. Pooled OS and PFS analysis favored the combination regimens other than sorafenib along. : Here, we present preliminary evidence for the comparative safety and efficacy of existing MTDs, ICIs, HAIC and their combinations in AHCC, which indicated that HAIC-oxaliplatin monotherapy has acceptable toxicity and efficacy and could be the cornerstone for future combination of systemic treatments in AHCC. Our findings might provide insight into the future design of multidisciplinary treatments in AHCC.
最近的几项3期试验报告了分子靶向药物（MTDs；索拉非尼、乐伐替尼）、免疫检查点抑制剂（ICIs；纳武单抗、帕博利珠单抗、阿替利珠单抗）、肝动脉灌注化疗（HAIC）及其联合方案在晚期肝细胞癌（AHCC）中的安全性可控且具有有前景的抗肿瘤活性；然而，这些方案之间缺乏直接比较。我们旨在全面回顾和比较不同的MTDs、ICIs、HAIC及其联合方案在AHCC中的疗效和安全性。评估了不良事件（AEs）、疾病控制率（DCRs）、客观缓解率（ORRs）、总生存期（OS）和无进展生存期（PFS）。索拉非尼、乐伐替尼、纳武单抗、帕博利珠单抗、阿替利珠单抗联合贝伐单抗、HAIC-顺铂联合索拉非尼、HAIC-奥沙利铂以及HAIC-奥沙利铂联合索拉非尼的1-5级/3-5级AE的合并发生率分别为98.0%/48.6%、98.3%/57.4%、91.4%/22.0%、96.4%/54.6%、98.2%/61.1%、86.3%/34.1%、88.9%/9.4%以及95.2%/53.2%，这表明纳武单抗在1-5级AE方面表现出最佳安全性，而HAIC-奥沙利铂单药治疗在3-5级AE方面排名最低。根据RECIST1.1标准，乐伐替尼（72.8%）、阿替利珠单抗联合贝伐单抗（73.6%）、HAIC-奥沙利铂（78.8%）以及HAIC-奥沙利铂联合索拉非尼（75.2%）的DCR高于索拉非尼（57.3%）、纳武单抗（33.9%）和帕博利珠单抗（62.3%），而只有基于HAIC-奥沙利铂的治疗方案显示出比其他方案更高的ORR。汇总的OS和PFS分析支持除索拉非尼之外的联合方案。在此，我们提供了现有MTDs、ICIs、HAIC及其联合方案在AHCC中比较安全性和疗效的初步证据，这表明HAIC-奥沙利铂单药治疗具有可接受的毒性和疗效，可能成为未来AHCC全身治疗联合方案的基石。我们的研究结果可能为AHCC多学科治疗的未来设计提供见解。
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