ASCO GI 2025丨阿替利珠单抗联合贝伐珠单抗治疗肝细胞癌的最新进展

健康   2025-01-26 18:02   北京  



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在2025年美国临床肿瘤学会胃肠道肿瘤研讨会(ASCO GI 2025)上,阿替利珠单抗联合贝伐珠单抗在肝细胞癌(HCC)治疗中的两项研究备受关注(摘要号:521和600)。《肿瘤瞭望消化时讯》特将两项研究内容整理,以飨读者。




研究一:一项评估阿替利珠单抗联合贝伐珠单抗治疗对初始不可切除肝细胞癌进行切除术有效性(RACB研究)的多中心前瞻性研究的短期结局

背景


IMbrave150研究表明,阿替利珠单抗联合贝伐珠单抗(atezo+bev)在无进展生存期和总生存期方面优于索拉非尼,已成为不可切除HCC的一线推荐全身治疗策略。RACB研究旨在评估atezo+bev在初始不可切除HCC患者中实现转化手术的疗效。本次报告为RACB研究的短期结果。

方法


RACB研究是一项前瞻性、单臂、多中心的Ⅱ期临床试验,旨在评估atezo+bev治疗在技术上或肿瘤学上不可切除的HCC患者中实现转化手术的效果。纳入标准为未接受过全身化疗、根据RECIST 1.1版本标准至少有一个靶病灶的不可切除HCC患者。患者每三周接受一次阿替利珠单抗(1200 mg)联合贝伐珠单抗(15 mg/kg)治疗。若在12周的影像学评估中达到可切除标准,则改用阿替利珠单抗单药治疗,随后进行手术。主要终点为无进展生存期,次要终点包括总体缓解率、总生存期、切除率、根治性切除率、R0切除率,以及atezo+bev治疗后15分钟ICG滞留率。本研究已在日本临床试验注册系统(jRCTs051210148)中登记。


结果


2022年3月至2024年3月期间,共有来自17个中心的55例患者入组。因病灶不符合要求或其他原因,4例患者被排除。最终50例患者纳入疗效评估集。38例患者(76.0%)存在大血管侵犯。6例患者(12.0%)存在肝外转移,其中2例患者(4.0%)有异时性肝外转移,无肝内病灶。根据RECIST标准,完全缓解率为0%,部分缓解率为13%;根据mRECIST标准,完全缓解率为2.2%,部分缓解率为26.1%。总体切除率为48%(24例)。在手术切除的患者中,R0切除21例(87.5%),R1切除1例(4.2%),R2切除2例(8.3%)。根据Clavien-Dindo分类,≥3级并发症包括胆漏3例、感染2例、吻合口漏1例和咯血1例。未发生手术相关死亡。在51例纳入安全性分析的患者中,34例(66.7%)发生不良事件,其中16例为3级或以上,包括1例4级上消化道出血、1例4级脑病,以及1例在接受1周期atezo+bev治疗后发生的意外死亡。

结论


本次RACB研究的短期结果表明,对于初始不可切除的HCC患者,atezo+bev治疗后进行转化手术是可行的。根据mRECIST标准,atezo+bev的缓解率与IMbrave150研究相似,切除率为48%。未来仍需对严重不良事件进行密切监测以确保安全性。



研究二:阿替利珠单抗联合贝伐珠单抗治疗晚期肝细胞癌患者的长期生存结局

背景


免疫治疗联合方案,如阿替利珠单抗联合atezo+bev或STRIDE,已成为晚期HCC患者的标准一线治疗。研究表明,双免疫治疗能够为部分患者带来持续的肿瘤缓解和长期生存获益。然而,尽管已有部分患者表现出良好的长期疗效,atezo+bev治疗后的长期生存结局仍需进一步评估。

方法


本研究对台湾四家医疗中心的病历进行分析,纳入了2018年1月至2021年5月期间接受atezo+bev治疗的Child-Pugh A类肝功能储备的晚期HCC患者,以评估其长期随访后的生存状况。

结果


本研究共纳入54例患者,其中男性占90.7%,中位年龄为65岁。主要的肝炎病因是病毒性肝炎(92.6%),其中68.5%为慢性乙型肝炎。经过中位期为61.9个月的随访,中位总生存期(OS)为21.0个月(95%CI:10.4~31.6个月)。3年、4年和5年的OS分别为36.4%、25.7%和25.7%。对于获得一定程度疾病缓解的患者(N=19,34.5%)或疾病得到控制的患者(N=44,80.0%),3年、4年和5年的OS率见表1。在单因素分析中,较年轻的患者(≤70岁)、无肝内肿瘤、无大血管侵犯(MVI)、ALBI等级1与OS超过3年相关。在多因素分析中,调整性别、病毒性肝炎、大血管侵犯、肝外转移和初始甲胎蛋白(AFP)>400 ng/ml后,肝内肿瘤缺失(OR=5.36,P=0.047)和ALBI 1级(与2级相比,OR=10.02,P=0.037)仍然是OS超过3年的独立预测因子。

表1. 按治疗反应分层的接受atezo+bev治疗患者的3年、4年和5年OS.

注:Responder:指在atezo+bev治疗后获得完全缓解(CR)或部分缓解(PR)的患者。

Disease control:包括所有患者以及经atezo+bev治疗后获得疾病稳定(SD)的患者。


结论


在晚期HCC患者中,atezo+bev治疗使得绝大多数患者实现长期生存获益,尤其是对于治疗反应良好的患者。无肝内肿瘤和良好的肝功能储备是预测长期生存的重要因素。







摘要原文


A multicenter prospective study to evaluate the efficacy of resection for initially unresectable hepatocellular carcinoma after atezolizumab combined with bevacizumab (the RACB study): Short-term outcomes.

Maho Takayama|Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo

Background:The IMbrave150 study showed that atezolizumab plus bevacizumab (atezo+bev) is superior to sorafenib in progression-free survival and overall survival, making it the recommended first-line systemic therapy for unresectable hepatocellular carcinoma (HCC). The RACB study was scheduled to evaluate the efficacy of atezo+bev in achieving conversion surgery for initially unresectable HCC. This time, we report the short-term outcomes of the RACB study.

Methods:This prospective, single-arm, multicenter Phase II trial evaluates atezo+bev to achieve conversion surgery in patients with technically or oncologically unresectable HCC. Eligible patients had unresectable HCC without prior systemic chemotherapy and at least one target lesion based on RECIST ver1.1. Patients received atezolizumab (1200 mg) plus bevacizumab (15 mg/kg) every three weeks. If resectable on radiological assessment at 12 weeks, atezolizumab monotherapy was given followed by surgery. The primary endpoint was the progression-free survival. The secondary endpoints included the overall response rate, overall survival, resection rate, curative resection rate, on-protocol resection rate, and ICG retention rate at 15 min after atezo+bev therapy. The study is registered with the Japan Registry of Clinical Trials (jRCTs051210148).

Results:Between March 2022 and March 2024, 55 patients from 17 centers were enrolled. Four patients were excluded due to ineligible lesions or other reasons. A total of 50 patients were included in the efficacy evaluation set. Macrovascular invasion and extrahepatic metastases were observed in 38 (76.0%) and 6 patients (12.0%), respectively. Two patients (4.0%) had metachronous extrahepatic metastases without intrahepatic tumors. The complete and partial response rates were 0% and 13% based on RECIST, and 2.2% and 26.1% based on mRECIST. The overall resection rate was 48%, corresponding to 24 cases. R0, R1, and R2 resections were performed in 21 (87.5%), 1 (4.2%), and 2 (8.3%) patients, respectively. Complications ≥Grade III according to the Clavien-Dindo classification included 3 bile leakages, 2 infections, 1 anastomotic leakage, and 1 hemoptysis. There were no surgery-related deaths. Of the 51 patients included in the safety analysis set, adverse events occurred in 34 cases (66.7%), with 16 Grade 3 or higher instances with one Grade 4 upper gastrointestinal bleeding, 1 Grade 4 encephalopathy, and 1 unexpected death after 1 cycle of atezo+bev.

Conclusions:The RACB study's short-term outcomes demonstrated the feasibility of conversion surgery after atezo+bev in patients with initially unresectable HCC. The response rate of atezo+bev, as measured by mRECIST, was similar to IMbrave150, with a 48% resection rate, though careful monitoring of severe adverse events is essential.

Long-term survival outcomes of atezolizumab plus bevacizumab treatment in patients with advanced hepatocellular carcinoma.

Abstract #600

Ching-Tso Chen|Department of Oncology, National Taiwan University Hospital Hsinchu Branch

Background:

Immunotherapy combinations such as atezolizumab plus bevacizumab (Atezo-Bev) or STRIDE have been established as standard therapies for patients with advanced hepatocellular carcinoma (HCC). After dual immunotherapy treatment, durable responders and long-term survivors had been reported. However, the longevity of such outcomes following Atezo-Bev treatment remains to be evaluated.

Methods:

We analyzed medical records of four medical centers in Taiwan for patients with Child-Pugh class A liver reserve who received first-line Atezo-Bev treatment for advanced HCC from January 2018 to May 2021, to evaluate their survival outcomes after a long-term follow-up.

Results:

We enrolled 54 patients, predominantly male (90.7%) with the median age of 65 years. The main hepatitis etiology was viral hepatitis (92.6%), including 68.5% chronic hepatitis B. After a median follow-up of 61.9 months, the median overall survival (OS) was 21.0 months (95% confidence interval 10.4 – 31.6 months). The 3-year, 4-year and 5-year OS rate was 36.4%, 25.7% and 25.7%, respectively. For patients with tumor response (N = 19, 34.5%) or disease control (N = 44, 80.0%), the 3-year, 4-year, and 5-year OS rates are listed at Table 1. In univariate analysis, younger age (≤ 70 years), absence of intrahepatic tumor, lack of macrovascular invasion (MVI), and ALBI grade 1 were associated with an OS > 3 years. In multivariate analysis, after adjusting sex, viral hepatitis, MVI, extrahepatic spread, and initial alpha-fetoprotein >400 ng/ml, the absence of intrahepatic tumor (Odds ratio [OR] = 5.36,?p?= 0.047) and ALBI grade 1 (vs grade 2, OR = 10.02, p = 0.037) remained independent predictors for OS > 3 years.

Conclusions:

In patients with advanced HCC, Atezo-Bev treatment led to a notable proportion achieving long-term survival, especially in patients with good response to the treatment. Absence of intrahepatic tumors and preserved liver function are predictive of prolonged survival.

3-year, 4-year and 5-year OS rate of patients who receive Atezo-Bev treatment, stratified by treatment response.

Landmark survival OS rate (%) by treatment response

Disease control Responder

3 years 35.6 52.2

4 years 30.3 52.2

5 years 30.3 47.7

Responder: patients who achieved a best response of complete response or partial response after treatment with Atezo-Bev.

Disease control: includes responders and patients who achieved a best response of stable disease following Atezo-Bev treatment.


来源:肿瘤瞭望消化时讯




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ioncology
《肿瘤瞭望》于2014年初创刊,由著名肿瘤科专家徐兵河院士担任总编辑,以“同步传真国际肿瘤进展”为办刊宗旨,以循证医学理念为指导思想,采用全媒体组合报道模式,致力于为国内广大肿瘤临床、教研人员搭建一座与国际接轨的桥梁。
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