First-Line Immune Checkpoint Inhibitor-Based Sequential Therapies for Advanced Hepatocellular Carcinoma: Rationale for Future Trials

Introduction: Atezolizumab (ATEZO) plus bevacizumab (BEVA) represents the new standard of care for the treatment of advanced hepatocellular carcinoma (HCC). However, the choice of the second-line treatment after the failure of immunotherapy-based first-line remains elusive. Taking into account the w...

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Autores principales:	Giuseppe Cabibbo, Maria Reig, Ciro Celsa, Ferran Torres, Salvatore Battaglia, Marco Enea, Giacomo Emanuele Maria Rizzo, Salvatore Petta, Vincenza Calvaruso, Vito Di Marco, Antonio Craxì, Amit G. Singal, Jordi Bruix, Calogero Cammà
Formato:	article
Lenguaje:	EN
Publicado:	Karger Publishers 2021
Materias:	hepatocellular carcinoma sequential treatment immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/49f9c3951aad466793506f22ced773ef
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spelling	oai:doaj.org-article:49f9c3951aad466793506f22ced773ef2021-12-02T12:40:23ZFirst-Line Immune Checkpoint Inhibitor-Based Sequential Therapies for Advanced Hepatocellular Carcinoma: Rationale for Future Trials2235-17951664-555310.1159/000520278https://doaj.org/article/49f9c3951aad466793506f22ced773ef2021-11-01T00:00:00Zhttps://www.karger.com/Article/FullText/520278https://doaj.org/toc/2235-1795https://doaj.org/toc/1664-5553Introduction: Atezolizumab (ATEZO) plus bevacizumab (BEVA) represents the new standard of care for the treatment of advanced hepatocellular carcinoma (HCC). However, the choice of the second-line treatment after the failure of immunotherapy-based first-line remains elusive. Taking into account the weaknesses of the available evidence, we developed a simulation model based on available phase III randomized clinical trials (RCTs) to identify optimal risk/benefit sequential strategies. Methods: A Markov model was built to estimate the overall survival (OS) of sequential first- and second-line systemic treatments. Sequences starting with first-line ATEZO plus BEVA followed by 5 second-line treatments (sorafenib [SORA], lenvatinib [LENVA], regorafenib, cabozantinib, and ramucirumab) were compared. The probability of transition between states (initial treatment, cancer progression, and death) was derived from RCTs. Life-year gained (LYG) was the main outcome. Rates of severe adverse events (SAEs) (≥ grade 3) were calculated. The incremental safety-effectiveness ratio (ISER) was calculated as the difference in probability of SAEs divided by LYG between the 2 most effective sequences. Results: ATEZO plus BEVA followed by LENVA (median OS, 24 months) or SORA (median OS, 23 months) was the most effective sequence, producing a LYG of 0.50 and 0.42 year, respectively. ATEZO plus BEVA followed by SORA was the safest sequence (SAEs 63%). At a willingness-to-risk threshold of 10% of SAEs for LYG, ATEZO plus BEVA followed by second-line SORA was favored in 72% of cases, while at a threshold of 30% of SAEs for LYG, ATEZO plus BEVA followed by second-line LENVA was favored in 69% of cases. Conclusion: Our simulation model provides a strong rationale to support ongoing trials evaluating second-line tyrosine-kinase inhibitors after first-line ATEZO plus BEVA. Future evidence from ongoing RCTs and prospective real-world studies are needed to prove the net health benefit of sequential treatment options for advanced HCC.Giuseppe CabibboMaria ReigCiro CelsaFerran TorresSalvatore BattagliaMarco EneaGiacomo Emanuele Maria RizzoSalvatore PettaVincenza CalvarusoVito Di MarcoAntonio CraxìAmit G. SingalJordi BruixCalogero CammàKarger Publishersarticlehepatocellular carcinomasequential treatmentimmunotherapyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLiver Cancer, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hepatocellular carcinoma sequential treatment immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	hepatocellular carcinoma sequential treatment immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Giuseppe Cabibbo Maria Reig Ciro Celsa Ferran Torres Salvatore Battaglia Marco Enea Giacomo Emanuele Maria Rizzo Salvatore Petta Vincenza Calvaruso Vito Di Marco Antonio Craxì Amit G. Singal Jordi Bruix Calogero Cammà First-Line Immune Checkpoint Inhibitor-Based Sequential Therapies for Advanced Hepatocellular Carcinoma: Rationale for Future Trials
description	Introduction: Atezolizumab (ATEZO) plus bevacizumab (BEVA) represents the new standard of care for the treatment of advanced hepatocellular carcinoma (HCC). However, the choice of the second-line treatment after the failure of immunotherapy-based first-line remains elusive. Taking into account the weaknesses of the available evidence, we developed a simulation model based on available phase III randomized clinical trials (RCTs) to identify optimal risk/benefit sequential strategies. Methods: A Markov model was built to estimate the overall survival (OS) of sequential first- and second-line systemic treatments. Sequences starting with first-line ATEZO plus BEVA followed by 5 second-line treatments (sorafenib [SORA], lenvatinib [LENVA], regorafenib, cabozantinib, and ramucirumab) were compared. The probability of transition between states (initial treatment, cancer progression, and death) was derived from RCTs. Life-year gained (LYG) was the main outcome. Rates of severe adverse events (SAEs) (≥ grade 3) were calculated. The incremental safety-effectiveness ratio (ISER) was calculated as the difference in probability of SAEs divided by LYG between the 2 most effective sequences. Results: ATEZO plus BEVA followed by LENVA (median OS, 24 months) or SORA (median OS, 23 months) was the most effective sequence, producing a LYG of 0.50 and 0.42 year, respectively. ATEZO plus BEVA followed by SORA was the safest sequence (SAEs 63%). At a willingness-to-risk threshold of 10% of SAEs for LYG, ATEZO plus BEVA followed by second-line SORA was favored in 72% of cases, while at a threshold of 30% of SAEs for LYG, ATEZO plus BEVA followed by second-line LENVA was favored in 69% of cases. Conclusion: Our simulation model provides a strong rationale to support ongoing trials evaluating second-line tyrosine-kinase inhibitors after first-line ATEZO plus BEVA. Future evidence from ongoing RCTs and prospective real-world studies are needed to prove the net health benefit of sequential treatment options for advanced HCC.
format	article
author	Giuseppe Cabibbo Maria Reig Ciro Celsa Ferran Torres Salvatore Battaglia Marco Enea Giacomo Emanuele Maria Rizzo Salvatore Petta Vincenza Calvaruso Vito Di Marco Antonio Craxì Amit G. Singal Jordi Bruix Calogero Cammà
author_facet	Giuseppe Cabibbo Maria Reig Ciro Celsa Ferran Torres Salvatore Battaglia Marco Enea Giacomo Emanuele Maria Rizzo Salvatore Petta Vincenza Calvaruso Vito Di Marco Antonio Craxì Amit G. Singal Jordi Bruix Calogero Cammà
author_sort	Giuseppe Cabibbo
title	First-Line Immune Checkpoint Inhibitor-Based Sequential Therapies for Advanced Hepatocellular Carcinoma: Rationale for Future Trials
title_short	First-Line Immune Checkpoint Inhibitor-Based Sequential Therapies for Advanced Hepatocellular Carcinoma: Rationale for Future Trials
title_full	First-Line Immune Checkpoint Inhibitor-Based Sequential Therapies for Advanced Hepatocellular Carcinoma: Rationale for Future Trials
title_fullStr	First-Line Immune Checkpoint Inhibitor-Based Sequential Therapies for Advanced Hepatocellular Carcinoma: Rationale for Future Trials
title_full_unstemmed	First-Line Immune Checkpoint Inhibitor-Based Sequential Therapies for Advanced Hepatocellular Carcinoma: Rationale for Future Trials
title_sort	first-line immune checkpoint inhibitor-based sequential therapies for advanced hepatocellular carcinoma: rationale for future trials
publisher	Karger Publishers
publishDate	2021
url	https://doaj.org/article/49f9c3951aad466793506f22ced773ef
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First-Line Immune Checkpoint Inhibitor-Based Sequential Therapies for Advanced Hepatocellular Carcinoma: Rationale for Future Trials

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