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Optimizing Sequential Systemic Therapies for Advanced Hepatocellular Carcinoma: A Decision Analysis

Background: An optimal sequential systemic therapy for advanced hepatocellular carcinoma (HCC) has not been discovered. We developed a decision model based on available clinical trials to identify an optimal risk/benefit strategy for sequences of novel systemic agents. Methods: A Markov model was bu...

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Detalles Bibliográficos
Autores principales: Cabibbo, Giuseppe, Celsa, Ciro, Enea, Marco, Battaglia, Salvatore, Rizzo, Giacomo Emanuele Maria, Grimaudo, Stefania, Matranga, Domenica, Attanasio, Massimo, Bruzzi, Paolo, Craxì, Antonio, Cammà, Calogero
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464739/
https://www.ncbi.nlm.nih.gov/pubmed/32752060
http://dx.doi.org/10.3390/cancers12082132
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author Cabibbo, Giuseppe
Celsa, Ciro
Enea, Marco
Battaglia, Salvatore
Rizzo, Giacomo Emanuele Maria
Grimaudo, Stefania
Matranga, Domenica
Attanasio, Massimo
Bruzzi, Paolo
Craxì, Antonio
Cammà, Calogero
author_facet Cabibbo, Giuseppe
Celsa, Ciro
Enea, Marco
Battaglia, Salvatore
Rizzo, Giacomo Emanuele Maria
Grimaudo, Stefania
Matranga, Domenica
Attanasio, Massimo
Bruzzi, Paolo
Craxì, Antonio
Cammà, Calogero
author_sort Cabibbo, Giuseppe
collection PubMed
description Background: An optimal sequential systemic therapy for advanced hepatocellular carcinoma (HCC) has not been discovered. We developed a decision model based on available clinical trials to identify an optimal risk/benefit strategy for sequences of novel systemic agents. Methods: A Markov model was built to simulate overall survival (OS) among patients with advanced HCC. Three first-line (single-agent Sorafenib or Lenvatinib, and combination of Atezolizumab plus Bevacizumab) followed by five second-line treatments (Regorafenib, Cabozantinib, Ramucirumab, Nivolumab, Pembrolizumab) were compared in fifteen sequential strategies. The likelihood of transition between states (initial treatment, cancer progression, death) was derived from clinical trials. Life-year gained (LYG) was the main outcome. Rates of severe adverse events (SAEs) (≥grade 3) were calculated. The innovative measure, called incremental safety-effectiveness ratio (ISER), of the two best sequential treatments was calculated as the difference in probability of SAEs divided by LYG. Results: Lenvatinib followed by Nivolumab (median OS, 27 months) was the most effective sequence, producing a LYG of 0.75, while Atezolizumab plus Bevacizumab followed by Nivolumab was the safest sequence (SAEs 40%). Accordingly, the net health benefit assessed by ISER favored Lenvatinib followed by Nivolumab, compared to Atezolizumab plus Bevacizumab, followed by Nivolumab in 52% of cases. Conclusion: Further sequential clinical trials or large-scale real-world studies may prove useful to evaluate the net health benefit of the best sequential treatment for advanced HCC.
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spelling pubmed-74647392020-09-04 Optimizing Sequential Systemic Therapies for Advanced Hepatocellular Carcinoma: A Decision Analysis Cabibbo, Giuseppe Celsa, Ciro Enea, Marco Battaglia, Salvatore Rizzo, Giacomo Emanuele Maria Grimaudo, Stefania Matranga, Domenica Attanasio, Massimo Bruzzi, Paolo Craxì, Antonio Cammà, Calogero Cancers (Basel) Article Background: An optimal sequential systemic therapy for advanced hepatocellular carcinoma (HCC) has not been discovered. We developed a decision model based on available clinical trials to identify an optimal risk/benefit strategy for sequences of novel systemic agents. Methods: A Markov model was built to simulate overall survival (OS) among patients with advanced HCC. Three first-line (single-agent Sorafenib or Lenvatinib, and combination of Atezolizumab plus Bevacizumab) followed by five second-line treatments (Regorafenib, Cabozantinib, Ramucirumab, Nivolumab, Pembrolizumab) were compared in fifteen sequential strategies. The likelihood of transition between states (initial treatment, cancer progression, death) was derived from clinical trials. Life-year gained (LYG) was the main outcome. Rates of severe adverse events (SAEs) (≥grade 3) were calculated. The innovative measure, called incremental safety-effectiveness ratio (ISER), of the two best sequential treatments was calculated as the difference in probability of SAEs divided by LYG. Results: Lenvatinib followed by Nivolumab (median OS, 27 months) was the most effective sequence, producing a LYG of 0.75, while Atezolizumab plus Bevacizumab followed by Nivolumab was the safest sequence (SAEs 40%). Accordingly, the net health benefit assessed by ISER favored Lenvatinib followed by Nivolumab, compared to Atezolizumab plus Bevacizumab, followed by Nivolumab in 52% of cases. Conclusion: Further sequential clinical trials or large-scale real-world studies may prove useful to evaluate the net health benefit of the best sequential treatment for advanced HCC. MDPI 2020-07-31 /pmc/articles/PMC7464739/ /pubmed/32752060 http://dx.doi.org/10.3390/cancers12082132 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cabibbo, Giuseppe
Celsa, Ciro
Enea, Marco
Battaglia, Salvatore
Rizzo, Giacomo Emanuele Maria
Grimaudo, Stefania
Matranga, Domenica
Attanasio, Massimo
Bruzzi, Paolo
Craxì, Antonio
Cammà, Calogero
Optimizing Sequential Systemic Therapies for Advanced Hepatocellular Carcinoma: A Decision Analysis
title Optimizing Sequential Systemic Therapies for Advanced Hepatocellular Carcinoma: A Decision Analysis
title_full Optimizing Sequential Systemic Therapies for Advanced Hepatocellular Carcinoma: A Decision Analysis
title_fullStr Optimizing Sequential Systemic Therapies for Advanced Hepatocellular Carcinoma: A Decision Analysis
title_full_unstemmed Optimizing Sequential Systemic Therapies for Advanced Hepatocellular Carcinoma: A Decision Analysis
title_short Optimizing Sequential Systemic Therapies for Advanced Hepatocellular Carcinoma: A Decision Analysis
title_sort optimizing sequential systemic therapies for advanced hepatocellular carcinoma: a decision analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464739/
https://www.ncbi.nlm.nih.gov/pubmed/32752060
http://dx.doi.org/10.3390/cancers12082132
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