Conversion Ability of Immunotherapy in Hepatocellular Carcinoma: Insights from the International Converse Study

Alessandro Vitale; Jung Sun Kim; Giuseppe Cabibbo; Andrea Casadei-Gardini; Massimo Iavarone; Lorenza Rimassa; Francesca Romana Ponziani; Francesco Tovoli; Hong Jae Chon; Beodeul Kang; Chan Kim; Hiroshi Imaoka; Masafumi Ikeda; Masatoshi Kudo; Tomoko Aoki; Raffaella Tortora; Marco Guarracino; Bernardo Stefanini; Mariarosaria Marseglia; Alba Sparacino; Ciro Celsa; Mariangela Bruccoleri; Eleonora Alimenti; Fabio Marra; Claudia Campani; Sherrie Bhoori; Vincenzo Mazzaferro; Rodolfo Sacco; Antonio Facciorusso; Andrea Martini; Leonardo Stella; Lucia Cerrito; Hidenori Toyoda; Satoshi Yasuda; Federico Rossari; Margherita Rimini; Goki Suda; Takuya Sho; Gianluca Masi; Caterina Vivaldi; Tiziana Pressiani; Satoru Kakizaki; Atsushi Naganuma; Antonio Avallone; Anna Nappi; Gianpaolo Vidili; Caterina Soldà; Francesca Bergamo; David J Pinato; Filippo Pelizzaro; Francesco Giuseppe Foschi; Alice Secomandi; Francesco Verderame; Enrico Bronte; Erika Martinelli; Donatella Marino; Sara Grasselli; Andrea Olivani; Maurizia Rossana Brunetto; Francesco Damone; Andrea Mega; Luca Marzi; Emiliano Tamburini; Matteo Ramundo; Piera Federico; Bruno Daniele; Edoardo G Giannini; Andrea Pasta; Filomena Morisco; Maria Guarino; Celine Hoyek; Sara Boninsegna; Ajay Gupta; David Sacerdoti; Andrea Dalbeni; Irina Calvo Ramos; Jorge Adeva; Carlo Saitta; Concetta Pitrone; Maria Luisa Lentini Graziano; Nunzia Farella; Maria Rendina; Teresa Grassi; Maria Grazia Rodriquenz; Evaristo Maiello; José Presa; Inês Pinho; Yoichi Hiasa; Masashi Hirooka; Jocelin Chen; Gianluca Arrichiello; Carlo Aschele; Alessandro Furlanetto; Umberto Cillo

doi:10.1159/000547792

Conversion Ability of Immunotherapy in Hepatocellular Carcinoma: Insights from the International Converse Study

Alessandro Vitale
, Jung Sun Kim
, Giuseppe Cabibbo
, Andrea Casadei-Gardini
, Massimo Iavarone
, Lorenza Rimassa
, Francesca Romana Ponziani
, Francesco Tovoli
, Hong Jae Chon
, Beodeul Kang
, Chan Kim
, Hiroshi Imaoka
, Masafumi Ikeda
, Masatoshi Kudo
, Tomoko Aoki
, Raffaella Tortora
, Marco Guarracino
, Bernardo Stefanini
, Mariarosaria Marseglia
, Alba Sparacino

Ciro Celsa, Mariangela Bruccoleri, Eleonora Alimenti, Fabio Marra, Claudia Campani, Sherrie Bhoori, Vincenzo Mazzaferro, Rodolfo Sacco, Antonio Facciorusso, Andrea Martini, Leonardo Stella, Lucia Cerrito, Hidenori Toyoda, Satoshi Yasuda, Federico Rossari, Margherita Rimini, Goki Suda, Takuya Sho, Gianluca Masi, Caterina Vivaldi, Tiziana Pressiani, Satoru Kakizaki, Atsushi Naganuma, Antonio Avallone, Anna Nappi, Gianpaolo Vidili, Caterina Soldà, Francesca Bergamo, David J Pinato, Filippo Pelizzaro, Francesco Giuseppe Foschi, Alice Secomandi, Francesco Verderame, Enrico Bronte, Erika Martinelli, Donatella Marino, Sara Grasselli, Andrea Olivani, Maurizia Rossana Brunetto, Francesco Damone, Andrea Mega, Luca Marzi, Emiliano Tamburini, Matteo Ramundo, Piera Federico, Bruno Daniele, Edoardo G Giannini, Andrea Pasta, Filomena Morisco, Maria Guarino, Celine Hoyek, Sara Boninsegna, Ajay Gupta, David Sacerdoti, Andrea Dalbeni, Irina Calvo Ramos, Jorge Adeva, Carlo Saitta, Concetta Pitrone, Maria Luisa Lentini Graziano, Nunzia Farella, Maria Rendina, Teresa Grassi, Maria Grazia Rodriquenz, Evaristo Maiello, José Presa, Inês Pinho, Yoichi Hiasa, Masashi Hirooka, Jocelin Chen, Gianluca Arrichiello, Carlo Aschele, Alessandro Furlanetto, Umberto Cillo

Krankenhaus Bozen

University Hospital of Padova
CHA University School of Medicine
Universitätsklinik für Innere Medizin III (Division of Gastroenterology and Hepatology) Ao. Univ.Prof. Dr. Peter Ferenci
Humanitas University
Liver Unit
Kindai University Faculty of Medicine
UOC Epatologia - AORN A Cardarelli
Unit of Internal Medicine and Hepatology
Dipartimento di Medicina Sperimentale e Clinica
Division of HPB Surgery
Dipartimento di Gastroenterologia ed Endoscopia Digestiva
Padova University and University Hospital
Ogaki Municipal Hospital
Hokkaido University Graduate School of Medicine
University Hospital of Pisa
IRCCS Humanitas Clinical and Research Center-Humanitas Cancer Center
NHO Takasaki General Medical Center
Experimental Clinical Abdominal Oncology Unit
Unità di Epatologia
Veneto Institute of Oncology IOV-IRCCS
Imperial College London
Medicina Interna di Faenza (AUSL Romagna)
UOC di Oncologia Medica
UOC di Oncologia ed Ematologia
Ordine Mauriziano Hospital Turin
Infectious Diseases and Hepatology Unit
Reparto di Gastroenterologia
Tricase City Hospital
Medical Oncology Unit
Dipartimento di Medicina Clinica e Chirurgia
Mayo Clinic Hospital
IRCCS Sacro Cuore Don Calabria Hospital
Indraprastha Apollo Hospital
University of Verona and University and Hospital Trust (AOUI) of Verona
Kamillus-Klinik Internal Medicine
Doce de Octubre Universitary Hospital
Department of Medical Oncology
"G. Martino" University Hospital Messina
Cotugno Hospital AORN dei Colli
University and University Hospital Tübingen
Ehime University Graduate School of Medicine
University of Study of Campania
Dipartimento di Oncologia-SODc Ematologia

Publikation: Beitrag in Fachzeitschrift › Originalarbeit › Begutachtung

Abstract

INTRODUCTION: The potential for curative conversion with immunotherapy-based systemic treatment used with noncurative intent in patients with hepatocellular carcinoma (HCC) remains debated. This study aimed to provide a reliable epidemiological snapshot of response patterns to atezolizumab plus bevacizumab (AB) therapy, with a focus on curative conversion rates.

METHODS: Patients with HCC undergoing first-line noncurative AB or lenvatinib (LENV, used as reference) from 2019 to 2023 were included, using centre-level aggregate data from a broad international consortium. The primary endpoint was the curative conversion rate, differentiating potential conversion (PC) - when objective response (OR) resulted in a consistent decrease in tumour burden and alpha-fetoprotein levels - from actual conversion (AC), when OR led to curative treatment. Secondary endpoints included OR, under-conversion (UC; [PC - AC]/OR) rates, and crude survival rates of AC patients. A meta-analytic approach was employed to analyse aggregate data.

RESULTS: Forty-eight international centres treating 2,379 patients with HCC with a noncurative intent (1,401 with AB and 978 with LENV) were included. A significant discrepancy was observed between PC (16% and 13% for AB and LENV, p = 0.03) and AC rates (3% for both AB and LENV, p = 0.14). UC rates remained similarly high (40% and 36% for AB and LENV, p = 0.93), despite differing OR rates (29% and 24% for AB and LENV, p = 0.01). Subgroup and meta-regression analyses did not identify any clear treatment, centre, or patient patterns that explained the high UC rate. The 3-year survival rate for the 72 patients who underwent a curative conversion after AB was 93%.

CONCLUSIONS: Although patients treated with AB achieved higher OR and PC rates than those treated with LENV, AC remained similarly low, highlighting a potentially worrisome UC phenomenon in real life, also with novel immunotherapy-based combinations.

Originalsprache	Englisch
Seitenumfang	22
Fachzeitschrift	LIVER CANCER
Frühes Online-Datum	Aug. 2025
DOIs	https://doi.org/10.1159/000547792
Publikationsstatus	Veröffentlicht - 5 Aug. 2025

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10.1159/000547792

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Vitale, A., Kim, J. S., Cabibbo, G., Casadei-Gardini, A., Iavarone, M., Rimassa, L., Ponziani, F. R., Tovoli, F., Chon, H. J., Kang, B., Kim, C., Imaoka, H., Ikeda, M., Kudo, M., Aoki, T., Tortora, R., Guarracino, M., Stefanini, B., Marseglia, M., ... Cillo, U. (2025). Conversion Ability of Immunotherapy in Hepatocellular Carcinoma: Insights from the International Converse Study. LIVER CANCER. https://doi.org/10.1159/000547792

@article{7ddfd23683e4453bbd077d2347a69e0e,

title = "Conversion Ability of Immunotherapy in Hepatocellular Carcinoma: Insights from the International Converse Study",

abstract = "INTRODUCTION: The potential for curative conversion with immunotherapy-based systemic treatment used with noncurative intent in patients with hepatocellular carcinoma (HCC) remains debated. This study aimed to provide a reliable epidemiological snapshot of response patterns to atezolizumab plus bevacizumab (AB) therapy, with a focus on curative conversion rates.METHODS: Patients with HCC undergoing first-line noncurative AB or lenvatinib (LENV, used as reference) from 2019 to 2023 were included, using centre-level aggregate data from a broad international consortium. The primary endpoint was the curative conversion rate, differentiating potential conversion (PC) - when objective response (OR) resulted in a consistent decrease in tumour burden and alpha-fetoprotein levels - from actual conversion (AC), when OR led to curative treatment. Secondary endpoints included OR, under-conversion (UC; [PC - AC]/OR) rates, and crude survival rates of AC patients. A meta-analytic approach was employed to analyse aggregate data.RESULTS: Forty-eight international centres treating 2,379 patients with HCC with a noncurative intent (1,401 with AB and 978 with LENV) were included. A significant discrepancy was observed between PC (16\% and 13\% for AB and LENV, p = 0.03) and AC rates (3\% for both AB and LENV, p = 0.14). UC rates remained similarly high (40\% and 36\% for AB and LENV, p = 0.93), despite differing OR rates (29\% and 24\% for AB and LENV, p = 0.01). Subgroup and meta-regression analyses did not identify any clear treatment, centre, or patient patterns that explained the high UC rate. The 3-year survival rate for the 72 patients who underwent a curative conversion after AB was 93\%.CONCLUSIONS: Although patients treated with AB achieved higher OR and PC rates than those treated with LENV, AC remained similarly low, highlighting a potentially worrisome UC phenomenon in real life, also with novel immunotherapy-based combinations.",

author = "Alessandro Vitale and Kim, \{Jung Sun\} and Giuseppe Cabibbo and Andrea Casadei-Gardini and Massimo Iavarone and Lorenza Rimassa and Ponziani, \{Francesca Romana\} and Francesco Tovoli and Chon, \{Hong Jae\} and Beodeul Kang and Chan Kim and Hiroshi Imaoka and Masafumi Ikeda and Masatoshi Kudo and Tomoko Aoki and Raffaella Tortora and Marco Guarracino and Bernardo Stefanini and Mariarosaria Marseglia and Alba Sparacino and Ciro Celsa and Mariangela Bruccoleri and Eleonora Alimenti and Fabio Marra and Claudia Campani and Sherrie Bhoori and Vincenzo Mazzaferro and Rodolfo Sacco and Antonio Facciorusso and Andrea Martini and Leonardo Stella and Lucia Cerrito and Hidenori Toyoda and Satoshi Yasuda and Federico Rossari and Margherita Rimini and Goki Suda and Takuya Sho and Gianluca Masi and Caterina Vivaldi and Tiziana Pressiani and Satoru Kakizaki and Atsushi Naganuma and Antonio Avallone and Anna Nappi and Gianpaolo Vidili and Caterina Sold{\`a} and Francesca Bergamo and Pinato, \{David J\} and Filippo Pelizzaro and Foschi, \{Francesco Giuseppe\} and Alice Secomandi and Francesco Verderame and Enrico Bronte and Erika Martinelli and Donatella Marino and Sara Grasselli and Andrea Olivani and Brunetto, \{Maurizia Rossana\} and Francesco Damone and Andrea Mega and Luca Marzi and Emiliano Tamburini and Matteo Ramundo and Piera Federico and Bruno Daniele and Giannini, \{Edoardo G\} and Andrea Pasta and Filomena Morisco and Maria Guarino and Celine Hoyek and Sara Boninsegna and Ajay Gupta and David Sacerdoti and Andrea Dalbeni and \{Calvo Ramos\}, Irina and Jorge Adeva and Carlo Saitta and Concetta Pitrone and \{Lentini Graziano\}, \{Maria Luisa\} and Nunzia Farella and Maria Rendina and Teresa Grassi and Rodriquenz, \{Maria Grazia\} and Evaristo Maiello and Jos{\'e} Presa and In{\^e}s Pinho and Yoichi Hiasa and Masashi Hirooka and Jocelin Chen and Gianluca Arrichiello and Carlo Aschele and Alessandro Furlanetto and Umberto Cillo",

note = "Lehr-KH Ospedale di Bolzano, Bolzano, Italy",

year = "2025",

month = aug,

day = "5",

doi = "10.1159/000547792",

language = "English",

journal = "LIVER CANCER",

issn = "2235-1795",

}

Vitale, A, Kim, JS, Cabibbo, G, Casadei-Gardini, A, Iavarone, M, Rimassa, L, Ponziani, FR, Tovoli, F, Chon, HJ, Kang, B, Kim, C, Imaoka, H, Ikeda, M, Kudo, M, Aoki, T, Tortora, R, Guarracino, M, Stefanini, B, Marseglia, M, Sparacino, A, Celsa, C, Bruccoleri, M, Alimenti, E, Marra, F, Campani, C, Bhoori, S, Mazzaferro, V, Sacco, R, Facciorusso, A, Martini, A, Stella, L, Cerrito, L, Toyoda, H, Yasuda, S, Rossari, F, Rimini, M, Suda, G, Sho, T, Masi, G, Vivaldi, C, Pressiani, T, Kakizaki, S, Naganuma, A, Avallone, A, Nappi, A, Vidili, G, Soldà, C, Bergamo, F, Pinato, DJ, Pelizzaro, F, Foschi, FG, Secomandi, A, Verderame, F, Bronte, E, Martinelli, E, Marino, D, Grasselli, S, Olivani, A, Brunetto, MR, Damone, F, Mega, A, Marzi, L, Tamburini, E, Ramundo, M, Federico, P, Daniele, B, Giannini, EG, Pasta, A, Morisco, F, Guarino, M, Hoyek, C, Boninsegna, S, Gupta, A, Sacerdoti, D, Dalbeni, A, Calvo Ramos, I, Adeva, J, Saitta, C, Pitrone, C, Lentini Graziano, ML, Farella, N, Rendina, M, Grassi, T, Rodriquenz, MG, Maiello, E, Presa, J, Pinho, I, Hiasa, Y, Hirooka, M, Chen, J, Arrichiello, G, Aschele, C, Furlanetto, A & Cillo, U 2025, 'Conversion Ability of Immunotherapy in Hepatocellular Carcinoma: Insights from the International Converse Study', LIVER CANCER. https://doi.org/10.1159/000547792

TY - JOUR

T1 - Conversion Ability of Immunotherapy in Hepatocellular Carcinoma

T2 - Insights from the International Converse Study

AU - Vitale, Alessandro

AU - Kim, Jung Sun

AU - Cabibbo, Giuseppe

AU - Casadei-Gardini, Andrea

AU - Iavarone, Massimo

AU - Rimassa, Lorenza

AU - Ponziani, Francesca Romana

AU - Tovoli, Francesco

AU - Chon, Hong Jae

AU - Kang, Beodeul

AU - Kim, Chan

AU - Imaoka, Hiroshi

AU - Ikeda, Masafumi

AU - Kudo, Masatoshi

AU - Aoki, Tomoko

AU - Tortora, Raffaella

AU - Guarracino, Marco

AU - Stefanini, Bernardo

AU - Marseglia, Mariarosaria

AU - Sparacino, Alba

AU - Celsa, Ciro

AU - Bruccoleri, Mariangela

AU - Alimenti, Eleonora

AU - Marra, Fabio

AU - Campani, Claudia

AU - Bhoori, Sherrie

AU - Mazzaferro, Vincenzo

AU - Sacco, Rodolfo

AU - Facciorusso, Antonio

AU - Martini, Andrea

AU - Stella, Leonardo

AU - Cerrito, Lucia

AU - Toyoda, Hidenori

AU - Yasuda, Satoshi

AU - Rossari, Federico

AU - Rimini, Margherita

AU - Suda, Goki

AU - Sho, Takuya

AU - Masi, Gianluca

AU - Vivaldi, Caterina

AU - Pressiani, Tiziana

AU - Kakizaki, Satoru

AU - Naganuma, Atsushi

AU - Avallone, Antonio

AU - Nappi, Anna

AU - Vidili, Gianpaolo

AU - Soldà, Caterina

AU - Bergamo, Francesca

AU - Pinato, David J

AU - Pelizzaro, Filippo

AU - Foschi, Francesco Giuseppe

AU - Secomandi, Alice

AU - Verderame, Francesco

AU - Bronte, Enrico

AU - Martinelli, Erika

AU - Marino, Donatella

AU - Grasselli, Sara

AU - Olivani, Andrea

AU - Brunetto, Maurizia Rossana

AU - Damone, Francesco

AU - Mega, Andrea

AU - Marzi, Luca

AU - Tamburini, Emiliano

AU - Ramundo, Matteo

AU - Federico, Piera

AU - Daniele, Bruno

AU - Giannini, Edoardo G

AU - Pasta, Andrea

AU - Morisco, Filomena

AU - Guarino, Maria

AU - Hoyek, Celine

AU - Boninsegna, Sara

AU - Gupta, Ajay

AU - Sacerdoti, David

AU - Dalbeni, Andrea

AU - Calvo Ramos, Irina

AU - Adeva, Jorge

AU - Saitta, Carlo

AU - Pitrone, Concetta

AU - Lentini Graziano, Maria Luisa

AU - Farella, Nunzia

AU - Rendina, Maria

AU - Grassi, Teresa

AU - Rodriquenz, Maria Grazia

AU - Maiello, Evaristo

AU - Presa, José

AU - Pinho, Inês

AU - Hiasa, Yoichi

AU - Hirooka, Masashi

AU - Chen, Jocelin

AU - Arrichiello, Gianluca

AU - Aschele, Carlo

AU - Furlanetto, Alessandro

AU - Cillo, Umberto

N1 - Lehr-KH Ospedale di Bolzano, Bolzano, Italy

PY - 2025/8/5

Y1 - 2025/8/5

N2 - INTRODUCTION: The potential for curative conversion with immunotherapy-based systemic treatment used with noncurative intent in patients with hepatocellular carcinoma (HCC) remains debated. This study aimed to provide a reliable epidemiological snapshot of response patterns to atezolizumab plus bevacizumab (AB) therapy, with a focus on curative conversion rates.METHODS: Patients with HCC undergoing first-line noncurative AB or lenvatinib (LENV, used as reference) from 2019 to 2023 were included, using centre-level aggregate data from a broad international consortium. The primary endpoint was the curative conversion rate, differentiating potential conversion (PC) - when objective response (OR) resulted in a consistent decrease in tumour burden and alpha-fetoprotein levels - from actual conversion (AC), when OR led to curative treatment. Secondary endpoints included OR, under-conversion (UC; [PC - AC]/OR) rates, and crude survival rates of AC patients. A meta-analytic approach was employed to analyse aggregate data.RESULTS: Forty-eight international centres treating 2,379 patients with HCC with a noncurative intent (1,401 with AB and 978 with LENV) were included. A significant discrepancy was observed between PC (16% and 13% for AB and LENV, p = 0.03) and AC rates (3% for both AB and LENV, p = 0.14). UC rates remained similarly high (40% and 36% for AB and LENV, p = 0.93), despite differing OR rates (29% and 24% for AB and LENV, p = 0.01). Subgroup and meta-regression analyses did not identify any clear treatment, centre, or patient patterns that explained the high UC rate. The 3-year survival rate for the 72 patients who underwent a curative conversion after AB was 93%.CONCLUSIONS: Although patients treated with AB achieved higher OR and PC rates than those treated with LENV, AC remained similarly low, highlighting a potentially worrisome UC phenomenon in real life, also with novel immunotherapy-based combinations.

AB - INTRODUCTION: The potential for curative conversion with immunotherapy-based systemic treatment used with noncurative intent in patients with hepatocellular carcinoma (HCC) remains debated. This study aimed to provide a reliable epidemiological snapshot of response patterns to atezolizumab plus bevacizumab (AB) therapy, with a focus on curative conversion rates.METHODS: Patients with HCC undergoing first-line noncurative AB or lenvatinib (LENV, used as reference) from 2019 to 2023 were included, using centre-level aggregate data from a broad international consortium. The primary endpoint was the curative conversion rate, differentiating potential conversion (PC) - when objective response (OR) resulted in a consistent decrease in tumour burden and alpha-fetoprotein levels - from actual conversion (AC), when OR led to curative treatment. Secondary endpoints included OR, under-conversion (UC; [PC - AC]/OR) rates, and crude survival rates of AC patients. A meta-analytic approach was employed to analyse aggregate data.RESULTS: Forty-eight international centres treating 2,379 patients with HCC with a noncurative intent (1,401 with AB and 978 with LENV) were included. A significant discrepancy was observed between PC (16% and 13% for AB and LENV, p = 0.03) and AC rates (3% for both AB and LENV, p = 0.14). UC rates remained similarly high (40% and 36% for AB and LENV, p = 0.93), despite differing OR rates (29% and 24% for AB and LENV, p = 0.01). Subgroup and meta-regression analyses did not identify any clear treatment, centre, or patient patterns that explained the high UC rate. The 3-year survival rate for the 72 patients who underwent a curative conversion after AB was 93%.CONCLUSIONS: Although patients treated with AB achieved higher OR and PC rates than those treated with LENV, AC remained similarly low, highlighting a potentially worrisome UC phenomenon in real life, also with novel immunotherapy-based combinations.

U2 - 10.1159/000547792

DO - 10.1159/000547792

M3 - Original Article

C2 - 41063731

SN - 2235-1795

JO - LIVER CANCER

JF - LIVER CANCER

ER -

Conversion Ability of Immunotherapy in Hepatocellular Carcinoma: Insights from the International Converse Study

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