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
{"title":"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","authors":"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","doi":"10.1159/000535501","DOIUrl":null,"url":null,"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.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"24 1","pages":""},"PeriodicalIF":11.6000,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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\",\"authors\":\"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\",\"doi\":\"10.1159/000535501\",\"DOIUrl\":null,\"url\":null,\"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.\",\"PeriodicalId\":18156,\"journal\":{\"name\":\"Liver Cancer\",\"volume\":\"24 1\",\"pages\":\"\"},\"PeriodicalIF\":11.6000,\"publicationDate\":\"2023-11-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Liver Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000535501\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Liver Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000535501","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
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
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.
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.