仑伐替尼联合卡瑞利珠单抗与仑伐替尼单药作为不可切除肝细胞癌一线治疗的多中心回顾性队列研究

Lenvatinib Plus Camrelizumab vs. Lenvatinib Monotherapy as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Cohort Study.

作者信息

Li Qi, Cao Mengran, Yuan Guosheng, Cheng Xiao, Zang Mengya, Chen Ming, Hu Xiaoyun, Huang Jing, Li Rong, Guo Yabing, Ruan Jian, Chen Jinzhang

机构信息

State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, China.

出版信息

Front Oncol. 2022 Feb 24;12:809709. doi: 10.3389/fonc.2022.809709. eCollection 2022.

BACKGROUND

Combining an antiangiogenic agent with an anti-PD-1 agent is a promising strategy for unresectable hepatocellular carcinoma (HCC).

AIMS

To explore the effectiveness and tolerability of lenvatinib plus camrelizumab vs. lenvatinib monotherapy as a first-line treatment for unresectable HCC.

METHODS

This multicenter, retrospective cohort study included patients with unresectable HCC treated with oral lenvatinib 8 mg daily and intravenous camrelizumab 200 mg every 3 weeks (L+C group) or lenvatinib 12 mg or 8 mg daily (L group) in four Chinese centers between September 2018 and February 2020. Tumor response was evaluated according to RECIST 1.1 and mRECIST. The outcomes included objective response rate (ORR), overall survival (OS), 1-year OS rate, progression-free survival (PFS), and safety.

RESULTS

By March 31, 2021, 92 patients were finally included, with 48 and 44 in the L+C and L groups, respectively. ORR was significantly higher in the L+C group than in the L group (RECIST 1.1: 37.5% vs. 13.6%, P=0.009; mRECIST: 41.7% vs. 20.5%, P=0.029). Median OS and 95% confidence interval (CI) was 13.9 (13.3-18.3) months in the L group and not reached in the L+C group (P=0.015). The 1-year survival rate was 79.2% and 56.8% in the L+C and L groups, respectively. Median PFS was 10.3 (6.6-14.0) months and 7.5 (5.7-9.3) months in the L+C and L groups, respectively (P=0.0098). Combined therapy vs. monotherapy was independently associated with a prolonged OS (hazard ratio=0.380, 95% CI=: 0.196-0.739, P=0.004) and a prolonged PFS (hazard ratio=0.454, 95%CI=0.282-0.731, P=0.001). The safety profile was comparable between the two groups. The most common adverse event in the L+C and L groups was loss of appetite (41.7% vs. 40.9%, P=0.941). Three patients in the L+C group and two in the L group terminated treatment owing to adverse events.

CONCLUSION

First-line lenvatinib plus camrelizumab showed better effectiveness than lenvatinib alone in patients with unresectable HCC.

背景

抗血管生成药物与抗程序性死亡蛋白1（PD-1）药物联合使用，是不可切除肝细胞癌（HCC）的一种有前景的治疗策略。

目的

探讨乐伐替尼联合卡瑞利珠单抗与乐伐替尼单药治疗作为不可切除HCC一线治疗方案的有效性和耐受性。

方法

这项多中心回顾性队列研究纳入了2018年9月至2020年2月期间在中国四个中心接受治疗的不可切除HCC患者，这些患者接受每日口服8mg乐伐替尼和每3周静脉注射200mg卡瑞利珠单抗（L+C组），或每日口服12mg或8mg乐伐替尼（L组）。根据实体瘤疗效评价标准（RECIST）1.1和改良RECIST（mRECIST）评估肿瘤反应。观察指标包括客观缓解率（ORR）、总生存期（OS）、1年总生存率、无进展生存期（PFS）和安全性。

结果

截至2021年3月31日，最终纳入92例患者，L+C组和L组分别有48例和44例。L+C组的ORR显著高于L组（RECIST 1.1：37.5%对13.6%，P=0.009；mRECIST：41.7%对20.5%，P=0.029）。L组中位OS及95%置信区间（CI）为13.9（13.3 - 18.3）个月，L+C组未达到（P=0.015）。L+C组和L组的1年生存率分别为79.2%和56.8%。L+C组和L组的中位PFS分别为10.3（6.6 - 14.0）个月和7.5（5.7 - 9.3）个月（P=0.0098）。联合治疗与单药治疗相比，独立与延长的OS（风险比=0.380,95%CI=0.196 - 0.739,P=0.004）和延长的PFS（风险比=0.454,95%CI=0.282 - 0.731,P=0.001）相关。两组的安全性相当。L+C组和L组最常见的不良事件是食欲减退（41.7%对40.9%，P=0.941）。L+C组有3例患者和L组有2例患者因不良事件终止治疗。