Impact of Bevacizumab Being Skipped due to Adverse Events of Special Interest for Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab: An Exploratory Analysis of the Phase III IMbrave150 study

IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Liver Cancer Pub Date : 2023-11-28 DOI:10.1159/000535501
Masatoshi Kudo, Kaoru Tsuchiya, Y. Shao, R. Finn, Peter R. Galle, Michel Ducreux, Ann-Lii Cheng, Tatsuya Yamashita, Hironori Koga, R. Take, Kyoko Yamada, T. Asakawa, Yuki Nakagawa, Masafumi Ikeda
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Abstract

Introduction: The Phase III IMbrave150 study established atezolizumab + bevacizumab as the global standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis examined the impact of bevacizumab interruption due to bevacizumab adverse events of special interest (AESIs). Methods: Patients in IMbrave150 who were randomized to atezolizumab + bevacizumab and received treatment for ≥6 months (to reduce immortal time bias) were included in group A-1 if bevacizumab had ever been skipped due to bevacizumab AESIs or to group A-2 otherwise. Efficacy analyses included overall survival (OS) and progression-free survival (PFS) by whether bevacizumab was skipped (group A-1 vs A-2). PFS was evaluated per independent review facility (IRF)–assessed Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and HCC-modified RECIST (IRF-HCC mRECIST). Safety was also evaluated. Results: Of the 210 patients who received ≥6 months of atezolizumab + bevacizumab, 69 were assigned to group A-1 and 141 to A-2. At data cutoff (August 20, 2020), hazard ratio (HR) for OS was 1.04 (95% CI: 0.64, 1.69) for group A-1 vs A-2. HR for PFS was 1.07 (95% CI: 0.74, 1.55) per IRF-assessed RECIST 1.1 and 1.10 (95% CI: 0.76, 1.59; 15.5 vs 9.7 months) per IRF-HCC mRECIST for group A-1 vs A-2. Safety profiles for atezolizumab and bevacizumab were largely similar between groups. More group A-1 patients had grade 3/4 adverse events. A separate analysis investigating the impact of immortal time bias in patients who received ≥3 months of atezolizumab + bevacizumab supported the appropriateness of the ≥6-month landmark analysis. Discussion/Conclusion: Efficacy was similar between patients who skipped bevacizumab due to bevacizumab AESIs and those who did not. Although this comparison was nonrandomized and exploratory, results suggest that skipping bevacizumab due to bevacizumab AESIs did not considerably impact the efficacy and safety of atezolizumab + bevacizumab.
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因贝伐单抗不良事件而放弃贝伐单抗对接受阿特珠单抗加贝伐单抗治疗的不可切除肝细胞癌患者的影响:IMbrave150Ⅲ期研究的探索性分析
简介IMbrave150Ⅲ期研究将阿特珠单抗+贝伐单抗确立为不可切除肝细胞癌(HCC)患者的全球标准治疗方案。这项探索性分析研究了因贝伐单抗特别关注不良事件(AESIs)而中断贝伐单抗治疗的影响。 研究方法IMbrave150中随机接受阿特珠单抗+贝伐珠单抗治疗且治疗时间≥6个月(以减少不死时间偏倚)的患者,如果曾因贝伐珠单抗AESI而跳过贝伐珠单抗,则纳入A-1组,否则纳入A-2组。疗效分析包括总生存期(OS)和无进展生存期(PFS),按是否跳过贝伐珠单抗(A-1 组与 A-2 组)进行分析。PFS根据独立审查机构(IRF)评估的《实体瘤反应评估标准》(RECIST)1.1版和HCC修正版RECIST(IRF-HCC mRECIST)进行评估。此外,还对安全性进行了评估。 结果:在接受阿特珠单抗+贝伐单抗治疗≥6个月的210名患者中,69人被分配到A-1组,141人被分配到A-2组。在数据截止日(2020年8月20日),A-1组与A-2组的OS危险比(HR)为1.04(95% CI:0.64,1.69)。A-1组与A-2组的PFS的HR分别为1.07(95% CI:0.74,1.55)和1.10(95% CI:0.76,1.59;15.5个月与9.7个月)。阿特珠单抗和贝伐珠单抗的安全性在各组之间基本相似。更多的A-1组患者出现了3/4级不良事件。一项单独的分析调查了接受atezolizumab+贝伐珠单抗治疗≥3个月的患者中永恒时间偏差的影响,结果支持≥6个月的标志性分析的适当性。 讨论/结论:因贝伐珠单抗AESI而放弃贝伐珠单抗的患者与未放弃贝伐珠单抗的患者疗效相似。尽管这种比较是非随机的、探索性的,但结果表明,因贝伐珠单抗 AESI 而跳过贝伐珠单抗并不会对阿特珠单抗+贝伐珠单抗的疗效和安全性产生重大影响。
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来源期刊
Liver Cancer
Liver Cancer Medicine-Oncology
CiteScore
20.80
自引率
7.20%
发文量
53
审稿时长
16 weeks
期刊介绍: Liver Cancer is a journal that serves the international community of researchers and clinicians by providing a platform for research results related to the causes, mechanisms, and therapy of liver cancer. It focuses on molecular carcinogenesis, prevention, surveillance, diagnosis, and treatment, including molecular targeted therapy. The journal publishes clinical and translational research in the field of liver cancer in both humans and experimental models. It publishes original and review articles and has an Impact Factor of 13.8. The journal is indexed and abstracted in various platforms including PubMed, PubMed Central, Web of Science, Science Citation Index, Science Citation Index Expanded, Google Scholar, DOAJ, Chemical Abstracts Service, Scopus, Embase, Pathway Studio, and WorldCat.
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