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Determinants of Treatment Benefit and Post-Treatment Survival for Patients with Hepatocellular Carcinoma Enrolled in Second-Line Trials after the Failure of Sorafenib Treatment

Second-line treatments are standard care for advanced hepatocellular carcinoma (HCC) patients with preserved liver function who are intolerant of or progress on first-line therapy. However, determinants of treatment benefit and post-treatment survival (PTS) remain unknown. HCC patients previously tr...

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Autores principales: Personeni, Nicola, Pressiani, Tiziana, Zanuso, Valentina, Casadei-Gardini, Andrea, D’Alessio, Antonio, Valgiusti, Martina, Dadduzio, Vincenzo, Bergamo, Francesca, Soldà, Caterina, Rizzato, Mario Domenico, Giordano, Laura, Santoro, Armando, Rimassa, Lorenza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604940/
https://www.ncbi.nlm.nih.gov/pubmed/36294865
http://dx.doi.org/10.3390/jpm12101726
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author Personeni, Nicola
Pressiani, Tiziana
Zanuso, Valentina
Casadei-Gardini, Andrea
D’Alessio, Antonio
Valgiusti, Martina
Dadduzio, Vincenzo
Bergamo, Francesca
Soldà, Caterina
Rizzato, Mario Domenico
Giordano, Laura
Santoro, Armando
Rimassa, Lorenza
author_facet Personeni, Nicola
Pressiani, Tiziana
Zanuso, Valentina
Casadei-Gardini, Andrea
D’Alessio, Antonio
Valgiusti, Martina
Dadduzio, Vincenzo
Bergamo, Francesca
Soldà, Caterina
Rizzato, Mario Domenico
Giordano, Laura
Santoro, Armando
Rimassa, Lorenza
author_sort Personeni, Nicola
collection PubMed
description Second-line treatments are standard care for advanced hepatocellular carcinoma (HCC) patients with preserved liver function who are intolerant of or progress on first-line therapy. However, determinants of treatment benefit and post-treatment survival (PTS) remain unknown. HCC patients previously treated with sorafenib and enrolled in second-line clinical trials were pooled according to the investigational treatment received and the subsequent regulatory approval: approved targeted agents and immune checkpoint inhibitors (AT) or other agents (OT) not subsequently approved. Univariate and multivariate analyses using Cox proportional hazards models established relationships among treatments received, clinical variables, and overall survival (OS) or PTS. For 174 patients (80 AT; 94 OT) analyzed, baseline factors for longer OS in multivariate analysis were second-line AT, absence of both portal vein thrombosis and extrahepatic spread (EHS). Treatment with AT (versus OT) was associated with significantly longer OS among patients with EHS (p(interaction) = 0.005) and patients with low neutrophil-to-lymphocyte ratio (NLR; p(interaction) = 0.032). Median PTS was 4.0 months (95% CI 2.8–5.3). At second-line treatment discontinuation, alpha-fetoprotein (AFP) levels <400 ng/dl, albumin-bilirubin (ALBI) grade 1, and enrolment onto subsequent trials independently predicted longer PTS. Treatment with AT, PVT, and EHS were prognostic factors for OS, while AFP, ALBI grade and enrolment onto a third-line trial were prognostic for PTS. Presence of EHS and low NLR were predictors of greater OS benefit from AT.
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spelling pubmed-96049402022-10-27 Determinants of Treatment Benefit and Post-Treatment Survival for Patients with Hepatocellular Carcinoma Enrolled in Second-Line Trials after the Failure of Sorafenib Treatment Personeni, Nicola Pressiani, Tiziana Zanuso, Valentina Casadei-Gardini, Andrea D’Alessio, Antonio Valgiusti, Martina Dadduzio, Vincenzo Bergamo, Francesca Soldà, Caterina Rizzato, Mario Domenico Giordano, Laura Santoro, Armando Rimassa, Lorenza J Pers Med Article Second-line treatments are standard care for advanced hepatocellular carcinoma (HCC) patients with preserved liver function who are intolerant of or progress on first-line therapy. However, determinants of treatment benefit and post-treatment survival (PTS) remain unknown. HCC patients previously treated with sorafenib and enrolled in second-line clinical trials were pooled according to the investigational treatment received and the subsequent regulatory approval: approved targeted agents and immune checkpoint inhibitors (AT) or other agents (OT) not subsequently approved. Univariate and multivariate analyses using Cox proportional hazards models established relationships among treatments received, clinical variables, and overall survival (OS) or PTS. For 174 patients (80 AT; 94 OT) analyzed, baseline factors for longer OS in multivariate analysis were second-line AT, absence of both portal vein thrombosis and extrahepatic spread (EHS). Treatment with AT (versus OT) was associated with significantly longer OS among patients with EHS (p(interaction) = 0.005) and patients with low neutrophil-to-lymphocyte ratio (NLR; p(interaction) = 0.032). Median PTS was 4.0 months (95% CI 2.8–5.3). At second-line treatment discontinuation, alpha-fetoprotein (AFP) levels <400 ng/dl, albumin-bilirubin (ALBI) grade 1, and enrolment onto subsequent trials independently predicted longer PTS. Treatment with AT, PVT, and EHS were prognostic factors for OS, while AFP, ALBI grade and enrolment onto a third-line trial were prognostic for PTS. Presence of EHS and low NLR were predictors of greater OS benefit from AT. MDPI 2022-10-17 /pmc/articles/PMC9604940/ /pubmed/36294865 http://dx.doi.org/10.3390/jpm12101726 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Personeni, Nicola
Pressiani, Tiziana
Zanuso, Valentina
Casadei-Gardini, Andrea
D’Alessio, Antonio
Valgiusti, Martina
Dadduzio, Vincenzo
Bergamo, Francesca
Soldà, Caterina
Rizzato, Mario Domenico
Giordano, Laura
Santoro, Armando
Rimassa, Lorenza
Determinants of Treatment Benefit and Post-Treatment Survival for Patients with Hepatocellular Carcinoma Enrolled in Second-Line Trials after the Failure of Sorafenib Treatment
title Determinants of Treatment Benefit and Post-Treatment Survival for Patients with Hepatocellular Carcinoma Enrolled in Second-Line Trials after the Failure of Sorafenib Treatment
title_full Determinants of Treatment Benefit and Post-Treatment Survival for Patients with Hepatocellular Carcinoma Enrolled in Second-Line Trials after the Failure of Sorafenib Treatment
title_fullStr Determinants of Treatment Benefit and Post-Treatment Survival for Patients with Hepatocellular Carcinoma Enrolled in Second-Line Trials after the Failure of Sorafenib Treatment
title_full_unstemmed Determinants of Treatment Benefit and Post-Treatment Survival for Patients with Hepatocellular Carcinoma Enrolled in Second-Line Trials after the Failure of Sorafenib Treatment
title_short Determinants of Treatment Benefit and Post-Treatment Survival for Patients with Hepatocellular Carcinoma Enrolled in Second-Line Trials after the Failure of Sorafenib Treatment
title_sort determinants of treatment benefit and post-treatment survival for patients with hepatocellular carcinoma enrolled in second-line trials after the failure of sorafenib treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604940/
https://www.ncbi.nlm.nih.gov/pubmed/36294865
http://dx.doi.org/10.3390/jpm12101726
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