Xie Diyang, Sun Qiman, Wang Xiaoying, Zhou Jian, Fan Jia, Ren Zhenggang, Gao Qiang
Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China.
Institute of Biomedical Sciences, Fudan University, Shanghai, China.
Ann Transl Med. 2021 Apr;9(8):652. doi: 10.21037/atm-20-7037.
This study aimed to evaluate safety and efficacy of programmed death-1 (PD-1) inhibitor sintilimab plus tyrosine kinase inhibitors (TKI) in a real-word cohort of patients with unresectable hepatocellular carcinoma (uHCC).
A total of 60 patients treated with sintilimab plus TKI between February 2019 and December 2019 were enrolled. Radiological response was recorded by computed tomography (CT) or magnetic resonance imaging (MRI) at baseline and every 6-12 weeks after treatment initiation. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and HCC-specific modified RECIST (mRECIST).
As of the data cutoff on September 30st, 2020, the median duration of follow-up was 10.4 (4.3-23.9) months. The objective response rate (ORR) and disease control rate (DCR) were 36.7% (95% CI: 24.9-48.5%), 81.7% (95% CI: 71.9-91.5%) according to the RECIST 1.1, and 52.8% (95% CI: 39.1-66.5%), 83.0% (95% CI: 73.2-93.8%) according to mRECIST criteria. Among 36 HCC patients with multinodular HCC or locally-advanced HCC with portal vein tumor thrombus (PVTT), 14 patients received one session of transarterial chemoembolization (TACE) within 1 month before or after the combinational systemic therapies, and the rest 22 patients did not receive any local regional therapies. After propensity score matching, patients from the TACE group tended to have a longer PFS (median, 10.1 9.1 months, P=0.73) than those from the non-TACE group but without significant differences. A total of 8 patients received surgical resection after the combined systemic therapies and 3 patients achieved pathological CR. No recurrence or metastasis was observed in 6 patients. A total of 46 (76.7%) patients reported adverse event (AE) with any grade and 8 (13.3%) patients discontinued the combination therapy due to grade 3/4 severe adverse events.
PD-1-targeted immunotherapy sintilimab plus TKIs exhibited promising efficacy with tolerable toxicity in unresectable HCC. The addition of TACE to the combined systemic therapies also resulted in a favorable tumor control and safety. For select responders, surgical resection might be a choice for radical treatment.
本研究旨在评估程序性死亡受体1（PD-1）抑制剂信迪利单抗联合酪氨酸激酶抑制剂（TKI）在不可切除肝细胞癌（uHCC）真实世界队列中的安全性和疗效。
纳入2019年2月至2019年12月期间接受信迪利单抗联合TKI治疗的60例患者。在基线时以及治疗开始后每6-12周通过计算机断层扫描（CT）或磁共振成像（MRI）记录影像学反应。根据实体瘤疗效评价标准（RECIST）1.1和肝癌特异性改良RECIST（mRECIST）评估肿瘤反应。
截至2020年9月30日数据截止时，中位随访时间为10.4（4.3-23.9）个月。根据RECIST 1.1标准，客观缓解率（ORR）和疾病控制率（DCR）分别为36.7%（95%CI：24.9-48.5%）、81.7%（95%CI：71.9-91.5%）；根据mRECIST标准，分别为52.8%（95%CI：39.1-66.5%）、83.0%（95%CI：73.2-93.8%）。在36例多结节肝癌或伴有门静脉癌栓（PVTT）的局部晚期肝癌患者中，14例患者在联合全身治疗前或后1个月内接受了1次经动脉化疗栓塞术（TACE），其余22例患者未接受任何局部区域治疗。倾向评分匹配后，TACE组患者的无进展生存期（PFS）倾向于长于非TACE组患者（中位值，10.1对9.1个月，P=0.73），但差异无统计学意义。共有8例患者在联合全身治疗后接受了手术切除，3例患者达到病理完全缓解（CR）。6例患者未观察到复发或转移。共有46例（76.7%）患者报告了任何级别的不良事件（AE），8例（13.3%）患者因3/4级严重不良事件停用联合治疗。
PD-1靶向免疫治疗信迪利单抗联合TKIs在不可切除肝癌中显示出有前景的疗效且毒性可耐受。在联合全身治疗中加用TACE也能实现良好的肿瘤控制和安全性。对于部分缓解者，手术切除可能是根治性治疗的一种选择。
