Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): final analysis of a randomised, open-label, international, phase 3 study.

Here, we present the final analysis of overall survival, and updated data on progression-free survival, secondary efficacy endpoints, and safety.

在这里，我们提供了总生存期的最终分析，以及无进展生存期、次要疗效终点和安全性方面的最新数据。

Methods

This randomised, open-label, international phase 3 trial (CARES-310) was done at 95 study sites across 13 countries and regions.

这是一项随机、开放标签的国际III期临床试验（CARES-310），在13个国家和地区的95个研究地点进行。

Eligible patients were aged 18 years or older, with unresectable or metastatic hepatocellular carcinoma, no previous systemic treatment, and an Eastern Cooperative Oncology Group performance status of 0 or 1.

符合条件的患者年龄在18岁或以上，患有不可切除或转移性肝细胞癌，之前未接受过全身治疗，并且东部肿瘤协作组（ECOG）表现状态为0或1。

Participants were randomly assigned (1:1) using a centralised interactive response system to receive either camrelizumab 200 mg intravenously every 2 weeks plus rivoceranib 250 mg orally once daily or sorafenib 400 mg orally twice daily.

参与者通过中央互动式响应系统以1:1的比例随机分配，接受卡瑞利珠单抗200毫克静脉注射每两周一次加上瑞维鲁胺250毫克口服每日一次，或索拉非尼400毫克口服每日两次。

The primary endpoints were progression-free survival, as assessed by the blinded independent review committee per Response Evaluation Criteria in Solid Tumours version 1.1, and overall survival, assessed in the intention-to-treatpopulation.

主要终点是无进展生存期，由盲法独立评审委员会根据实体瘤反应评估标准版本1.1进行评估，以及在意向治疗人群中评估的总生存期。

Safety was assessed in all patients who received at least one dose of the study drugs.

所有接受至少一剂研究药物的患者均进行了安全性评估。

The study is complete and was registered with ClinicalTrials.gov, NCT03764293.

该研究已经完成，并已在ClinicalTrials.gov上注册，注册号为NCT03764293。

Results

Between June 28, 2019, and March 24, 2021, 543 patients (457 [84%] males; 450 [83%] were Asian) were randomly assigned to receive camrelizumab-rivoceranib (n=272) or sorafenib (n=271).

2019年6月28日至2021年3月24日期间，共有543名患者（男性457名[84%]；亚洲人450名[83%]）被随机分配接受卡瑞利珠单抗-瑞沃替尼（n=272）或索拉非尼（n=271）治疗。

At final analysis on June 14, 2023, the median follow-up was 22·1 months (IQR 11·9-30·3) in the camrelizumab-rivoceranib group and 14·9 months (7·2-28·3) in the sorafenib group.

截至2023年6月14日的最终分析显示，卡瑞利珠单抗-瑞沃替尼组的中位随访时间为22.1个月（四分位数间距11.9-30.3），而索拉非尼组为14.9个月（四分位数间距7.2-28.3）。

Median overall survivalwas 23·8 months (95% CI 20·6-27·2) with camrelizumab-rivoceranib and 15·2 months (13·2-18·5) with sorafenib (hazard ratio[HR] 0·64 [95% CI 0·52-0·79]; one-sided p<0·0001).

卡瑞利珠单抗-瑞沃替尼联合治疗组的中位总生存期为23.8个月（95%置信区间20.6-27.2），而索拉非尼单药治疗组为15.2个月（13.2-18.5）（风险比[HR] 0.64 [95%置信区间0.52-0.79]；单侧p<0.0001）。

Median progression-free survivalwas 5·6 months (95% CI 5·5-7·4) with camrelizumab-rivoceranib and 3·7 months (3·1-3·7) with sorafenib (HR 0·54 [0·44-0·67]; one-sided p<0·0001).

卡瑞利珠单抗-瑞沃替尼联合治疗组的中位无进展生存期为5.6个月（95%置信区间5.5-7.4），而索拉非尼单药治疗组为3.7个月（3.1-3.7）（风险比[HR] 0.54 [95%置信区间0.44-0.67]；单侧p<0.0001）。

The most common grade 3 or 4 treatment-related adverse events were hypertension (104 [38%] of 272 patients in the camrelizumab-rivoceranib group vs 40 [15%] of 269 patients in the sorafenib group), palmar-plantar erythrodysaesthesia syndrome (33 [12%] vs 42 [16%]), increased aspartate aminotransferase (47 [17%] vs 14 [5%]), and increased alanine aminotransferase (38 [14%] vs eight [3%]).

最常见的3级或4级治疗相关不良事件是高血压（camrelizumab-rivoceranib组272名患者中有104名[38%]，而sorafenib组269名患者中有40名[15%]），手掌-足底红斑角化症（33名[12%]对比42名[16%]），天冬氨酸氨基转移酶升高（47名[17%]对比14名[5%]），以及丙氨酸氨基转移酶升高（38名[14%]对比八名[3%]）。

Treatment-related serious adverse events were reported in 69 (25%) of 272 patients in the camrelizumab-rivoceranib group and 18 (7%) of 269 patients in the sorafenib group.

在camrelizumab-rivoceranib组的272名患者中有69名（25%）报告了治疗相关的严重不良事件，而在sorafenib组的269名患者中有18名（7%）报告了治疗相关的严重不良事件。

Treatment-related deaths occurred in one patient each in the camrelizumab-rivoceranib group (multiple organ dysfunction syndrome) and sorafenib group (respiratory failure and circulatory collapse).

在卡瑞利珠单抗-瑞沃西尼组和索拉非尼组中，各有1名患者发生了与治疗相关的死亡（卡瑞利珠单抗-瑞沃西尼组为多器官功能衰竭综合征，索拉非尼组为呼吸衰竭和循环衰竭）。

interpretation

At final analysis, camrelizumab plus rivoceranib continued to show clinically meaningful survival improvement compared with sorafenib, with manageable safety.

在最终分析中，卡瑞利珠单抗联合瑞沃西尼继续显示出与索拉非尼相比具有临床意义的生存期改善，且安全性可控。

The extended follow-up further confirmed the benefit-to-risk profile of camrelizumab plus rivoceranib, supporting the combination as a new first-line treatment option for unresectable hepatocellular carcinoma.

延长随访进一步确认了卡瑞利珠单抗联合瑞沃替尼的效益-风险比，支持了这一组合作为不可切除肝细胞癌新一线治疗方案的潜力。

funding

Jiangsu Hengrui Pharmaceuticals and Elevar Therapeutics.

江苏恒瑞医药和Elevar Therapeutics。