Safety and Efficacy of Atezolizumab/Bevacizumab in Patients with Hepatocellular Carcinoma and Impaired Liver Function: A Systematic Review and Meta-Analysis
Abstract Background: Safety and outcome of atezolizumab/bevacizumab in Child-Pugh B patients with hepatocellular carcinoma (HCC) have not been completely characterized. Objectives: In this study, we aimed at addressing safety and efficacy of atezolizumab/bevacizumab in Child-Pugh B patients by revie...
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| Veröffentlicht in: | Liver cancer (Basel ) 2024-06, Vol.13 (3), p.235-245 |
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| creator | Pasta, Andrea Calabrese, Francesco Jaffe, Ariel Labanca, Sara Marenco, Simona Pieri, Giulia Plaz Torres, Maria Corina Strazzabosco, Mario Giannini, Edoardo G. |
| description | Abstract
Background: Safety and outcome of atezolizumab/bevacizumab in Child-Pugh B patients with hepatocellular carcinoma (HCC) have not been completely characterized. Objectives: In this study, we aimed at addressing safety and efficacy of atezolizumab/bevacizumab in Child-Pugh B patients by reviewing the available data and analyzing them by meta-analysis. Methods: We compared the safety and efficacy of atezolizumab/becavizumab treatment in patients with unresectable HCC and various degrees of liver dysfunction. A total of 8 retrospective, non-randomized, cohort studies were included in this meta-analysis, for a total of 1,071 Child-Pugh A and 225 Child-Pugh B patients. The albumin-bilirubin (ALBI) grade was also used to assess liver function, when available. Results: Grade ≥3 adverse events were observed in 11.8% of Child-Pugh class A and 26.8% class B patients (p = 0.0001), with an odds ratio (OR) of 0.43 (confidence interval [CI] 0.21–0.90; p = 0.02). Progression-free survival (PFS) at both 6 months (4.90 ± 2.08 vs. 4.75 ± 2.08 months; p = 0.0004) and 12 months (8.83 ± 2.32 vs. 7.26 ± 2.33 months; p = 0.002) was lower in Child-Pugh class B patients. A trend toward a higher objective response rate (ORR) was observed in Child-Pugh class A patients (219/856, 25.6%) as compared to Child-Pugh class B patients (25/138, 18.1%; p = 0.070), while the probability of obtaining an ORR was significantly greater in Child-Pugh A patients (OR 1.79, CI 1.12–2.86; p = 0.02). Median overall survival (OS) was 16.8 ± 2.0 and 6.8 ± 3.2 months in Child-Pugh A and B patients, respectively (mean difference 9.06 months, CI 7.01–11.1, p < 0.0001). Lastly, OS was longer in patients with ALBI grades 1–2 than in those with grade 3 (8.3 ± 11.4 vs. 3.3 ± 5.0 months, p = 0.0008). Conclusions: Oncological efficacy of atezolizumab/bevacizumab is moderate in Child-Pugh class B patients, and the shorter PFS and OS associated with the greater likelihood of experiencing treatment-related adverse events observed in these patients suggest great caution and individualization of treatment, possibly with the support of the ALBI grade. |
| doi_str_mv | 10.1159/000533991 |
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Background: Safety and outcome of atezolizumab/bevacizumab in Child-Pugh B patients with hepatocellular carcinoma (HCC) have not been completely characterized. Objectives: In this study, we aimed at addressing safety and efficacy of atezolizumab/bevacizumab in Child-Pugh B patients by reviewing the available data and analyzing them by meta-analysis. Methods: We compared the safety and efficacy of atezolizumab/becavizumab treatment in patients with unresectable HCC and various degrees of liver dysfunction. A total of 8 retrospective, non-randomized, cohort studies were included in this meta-analysis, for a total of 1,071 Child-Pugh A and 225 Child-Pugh B patients. The albumin-bilirubin (ALBI) grade was also used to assess liver function, when available. Results: Grade ≥3 adverse events were observed in 11.8% of Child-Pugh class A and 26.8% class B patients (p = 0.0001), with an odds ratio (OR) of 0.43 (confidence interval [CI] 0.21–0.90; p = 0.02). Progression-free survival (PFS) at both 6 months (4.90 ± 2.08 vs. 4.75 ± 2.08 months; p = 0.0004) and 12 months (8.83 ± 2.32 vs. 7.26 ± 2.33 months; p = 0.002) was lower in Child-Pugh class B patients. A trend toward a higher objective response rate (ORR) was observed in Child-Pugh class A patients (219/856, 25.6%) as compared to Child-Pugh class B patients (25/138, 18.1%; p = 0.070), while the probability of obtaining an ORR was significantly greater in Child-Pugh A patients (OR 1.79, CI 1.12–2.86; p = 0.02). Median overall survival (OS) was 16.8 ± 2.0 and 6.8 ± 3.2 months in Child-Pugh A and B patients, respectively (mean difference 9.06 months, CI 7.01–11.1, p < 0.0001). Lastly, OS was longer in patients with ALBI grades 1–2 than in those with grade 3 (8.3 ± 11.4 vs. 3.3 ± 5.0 months, p = 0.0008). Conclusions: Oncological efficacy of atezolizumab/bevacizumab is moderate in Child-Pugh class B patients, and the shorter PFS and OS associated with the greater likelihood of experiencing treatment-related adverse events observed in these patients suggest great caution and individualization of treatment, possibly with the support of the ALBI grade.</description><identifier>ISSN: 2235-1795</identifier><identifier>EISSN: 1664-5553</identifier><identifier>DOI: 10.1159/000533991</identifier><identifier>PMID: 38756146</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>benefit ; Bias ; cirrhosis ; Etiology ; Hepatitis ; Immunotherapy ; Liver cancer ; Liver diseases ; Meta-Analysis ; Monoclonal antibodies ; Response rates ; survival ; Systematic review ; systemic treatment ; Targeted cancer therapy</subject><ispartof>Liver cancer (Basel ), 2024-06, Vol.13 (3), p.235-245</ispartof><rights>2023 The Author(s). Published by S. Karger AG, Basel</rights><rights>2023 The Author(s). Published by S. Karger AG, Basel.</rights><rights>2023 The Author(s). Published by S. Karger AG, Basel. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the associated terms available at: https://uk.sagepub.com/en-gb/eur/reusing-open-access-and-sage-choice-content</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-23d53dbc1b06749ba4ff8f60da95a44d17cc4bb73a3dabecda094acf94fc5e473</citedby><cites>FETCH-LOGICAL-c463t-23d53dbc1b06749ba4ff8f60da95a44d17cc4bb73a3dabecda094acf94fc5e473</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,2096,27612,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38756146$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pasta, Andrea</creatorcontrib><creatorcontrib>Calabrese, Francesco</creatorcontrib><creatorcontrib>Jaffe, Ariel</creatorcontrib><creatorcontrib>Labanca, Sara</creatorcontrib><creatorcontrib>Marenco, Simona</creatorcontrib><creatorcontrib>Pieri, Giulia</creatorcontrib><creatorcontrib>Plaz Torres, Maria Corina</creatorcontrib><creatorcontrib>Strazzabosco, Mario</creatorcontrib><creatorcontrib>Giannini, Edoardo G.</creatorcontrib><title>Safety and Efficacy of Atezolizumab/Bevacizumab in Patients with Hepatocellular Carcinoma and Impaired Liver Function: A Systematic Review and Meta-Analysis</title><title>Liver cancer (Basel )</title><addtitle>Liver Cancer</addtitle><description>Abstract
Background: Safety and outcome of atezolizumab/bevacizumab in Child-Pugh B patients with hepatocellular carcinoma (HCC) have not been completely characterized. Objectives: In this study, we aimed at addressing safety and efficacy of atezolizumab/bevacizumab in Child-Pugh B patients by reviewing the available data and analyzing them by meta-analysis. Methods: We compared the safety and efficacy of atezolizumab/becavizumab treatment in patients with unresectable HCC and various degrees of liver dysfunction. A total of 8 retrospective, non-randomized, cohort studies were included in this meta-analysis, for a total of 1,071 Child-Pugh A and 225 Child-Pugh B patients. The albumin-bilirubin (ALBI) grade was also used to assess liver function, when available. Results: Grade ≥3 adverse events were observed in 11.8% of Child-Pugh class A and 26.8% class B patients (p = 0.0001), with an odds ratio (OR) of 0.43 (confidence interval [CI] 0.21–0.90; p = 0.02). Progression-free survival (PFS) at both 6 months (4.90 ± 2.08 vs. 4.75 ± 2.08 months; p = 0.0004) and 12 months (8.83 ± 2.32 vs. 7.26 ± 2.33 months; p = 0.002) was lower in Child-Pugh class B patients. A trend toward a higher objective response rate (ORR) was observed in Child-Pugh class A patients (219/856, 25.6%) as compared to Child-Pugh class B patients (25/138, 18.1%; p = 0.070), while the probability of obtaining an ORR was significantly greater in Child-Pugh A patients (OR 1.79, CI 1.12–2.86; p = 0.02). Median overall survival (OS) was 16.8 ± 2.0 and 6.8 ± 3.2 months in Child-Pugh A and B patients, respectively (mean difference 9.06 months, CI 7.01–11.1, p < 0.0001). Lastly, OS was longer in patients with ALBI grades 1–2 than in those with grade 3 (8.3 ± 11.4 vs. 3.3 ± 5.0 months, p = 0.0008). Conclusions: Oncological efficacy of atezolizumab/bevacizumab is moderate in Child-Pugh class B patients, and the shorter PFS and OS associated with the greater likelihood of experiencing treatment-related adverse events observed in these patients suggest great caution and individualization of treatment, possibly with the support of the ALBI grade.</description><subject>benefit</subject><subject>Bias</subject><subject>cirrhosis</subject><subject>Etiology</subject><subject>Hepatitis</subject><subject>Immunotherapy</subject><subject>Liver cancer</subject><subject>Liver diseases</subject><subject>Meta-Analysis</subject><subject>Monoclonal antibodies</subject><subject>Response rates</subject><subject>survival</subject><subject>Systematic review</subject><subject>systemic treatment</subject><subject>Targeted cancer therapy</subject><issn>2235-1795</issn><issn>1664-5553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>M--</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptks9v0zAUgCMEYlXZgTtClnaBQ5gd23HMrVQbq1QEYnCOXvxjuCRxsZ1O3d_CH0vajB4Qvth6_t6nZ7-XZS8JfkcIl5cYY06plORJNiNlyXLOOX2azYqC8pwIyc-y8xg3I4YrjIUUz7MzWgleElbOst-3YE3aI-g1urLWKVB75C1aJPPgW_cwdNBcfjA7UNMZuR59geRMnyK6d-kHujFbSF6Zth1aCGgJQbned3BUrrotuGA0WrudCeh66FVyvn-PFuh2H5PpRpVCX83OmftjwieTIF_00O6jiy-yZxbaaM4f93n2_frq2_ImX3_-uFou1rliJU15QTWnulGkwaVgsgFmbWVLrEFyYEwToRRrGkGBamiM0oAlA2Uls4obJug8W01e7WFTb4PrIOxrD64-Bny4qyGMhbamJrziUHFRVbRh2FopCy2MLBrOJC1YNbreTK5t8L8GE1PduXj4HeiNH2JNMS_HdWjSPLv4B934IYxvP1ACcyyJICP1dqJU8DEGY08FElwfJqA-TcDIvn40Dk1n9In82-8ReDUBPyHcmXACTvkX_71er5YTUW-1pX8AXUPAzg</recordid><startdate>20240601</startdate><enddate>20240601</enddate><creator>Pasta, Andrea</creator><creator>Calabrese, Francesco</creator><creator>Jaffe, Ariel</creator><creator>Labanca, Sara</creator><creator>Marenco, Simona</creator><creator>Pieri, Giulia</creator><creator>Plaz Torres, Maria Corina</creator><creator>Strazzabosco, Mario</creator><creator>Giannini, Edoardo G.</creator><general>S. 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Background: Safety and outcome of atezolizumab/bevacizumab in Child-Pugh B patients with hepatocellular carcinoma (HCC) have not been completely characterized. Objectives: In this study, we aimed at addressing safety and efficacy of atezolizumab/bevacizumab in Child-Pugh B patients by reviewing the available data and analyzing them by meta-analysis. Methods: We compared the safety and efficacy of atezolizumab/becavizumab treatment in patients with unresectable HCC and various degrees of liver dysfunction. A total of 8 retrospective, non-randomized, cohort studies were included in this meta-analysis, for a total of 1,071 Child-Pugh A and 225 Child-Pugh B patients. The albumin-bilirubin (ALBI) grade was also used to assess liver function, when available. Results: Grade ≥3 adverse events were observed in 11.8% of Child-Pugh class A and 26.8% class B patients (p = 0.0001), with an odds ratio (OR) of 0.43 (confidence interval [CI] 0.21–0.90; p = 0.02). Progression-free survival (PFS) at both 6 months (4.90 ± 2.08 vs. 4.75 ± 2.08 months; p = 0.0004) and 12 months (8.83 ± 2.32 vs. 7.26 ± 2.33 months; p = 0.002) was lower in Child-Pugh class B patients. A trend toward a higher objective response rate (ORR) was observed in Child-Pugh class A patients (219/856, 25.6%) as compared to Child-Pugh class B patients (25/138, 18.1%; p = 0.070), while the probability of obtaining an ORR was significantly greater in Child-Pugh A patients (OR 1.79, CI 1.12–2.86; p = 0.02). Median overall survival (OS) was 16.8 ± 2.0 and 6.8 ± 3.2 months in Child-Pugh A and B patients, respectively (mean difference 9.06 months, CI 7.01–11.1, p < 0.0001). Lastly, OS was longer in patients with ALBI grades 1–2 than in those with grade 3 (8.3 ± 11.4 vs. 3.3 ± 5.0 months, p = 0.0008). Conclusions: Oncological efficacy of atezolizumab/bevacizumab is moderate in Child-Pugh class B patients, and the shorter PFS and OS associated with the greater likelihood of experiencing treatment-related adverse events observed in these patients suggest great caution and individualization of treatment, possibly with the support of the ALBI grade.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>38756146</pmid><doi>10.1159/000533991</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | benefit Bias cirrhosis Etiology Hepatitis Immunotherapy Liver cancer Liver diseases Meta-Analysis Monoclonal antibodies Response rates survival Systematic review systemic treatment Targeted cancer therapy |
| title | Safety and Efficacy of Atezolizumab/Bevacizumab in Patients with Hepatocellular Carcinoma and Impaired Liver Function: A Systematic Review and Meta-Analysis |
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