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.
Conversion Ability of Immunotherapy in Hepatocellular Carcinoma: Insights from the International Converse Study / A. Vitale, J.S. Kim, G. Cabibbo, A. Casadei-Gardini, M. Iavarone, L. Rimassa, F.R. Ponziani, F. Tovoli, H.J. Chon, B. Kang, C. Kim, H. Imaoka, M. Ikeda, M. Kudo, T. Aoki, R. Tortora, M. Guarracino, B. Stefanini, M. Marseglia, A. Sparacino, C. Celsa, M. Bruccoleri, E. Alimenti, F. Marra, C. Campani, S. Bhoori, V. Mazzaferro, R. Sacco, A. Facciorusso, A. Martini, L. Stella, L. Cerrito, H. Toyoda, S. Yasuda, F. Rossari, M. Rimini, G. Suda, T. Sho, G. Masi, C. Vivaldi, T. Pressiani, S. Kakizaki, A. Naganuma, A. Avallone, A. Nappi, G. Vidili, C. Soldà, F. Bergamo, D.J. Pinato, F. Pelizzaro, F.G. Foschi, A. Secomandi, F. Verderame, E. Bronte, E. Martinelli, D. Marino, S. Grasselli, A. Olivani, M.R. Brunetto, F. Damone, A. Mega, L. Marzi, E. Tamburini, M. Ramundo, P. Federico, B. Daniele, E.G. Giannini, A. Pasta, F. Morisco, M. Guarino, C. Hoyek, S. Boninsegna, A. Gupta, D. Sacerdoti, A. Dalbeni, I. Calvo Ramos, J. Adeva, C. Saitta, C. Pitrone, M.L. Lentini Graziano, N. Farella, M. Rendina, T. Grassi, M.G. Rodriquenz, E. Maiello, J. Presa, I. Pinho, Y. Hiasa, M. Hirooka, J. Chen, G. Arrichiello, C. Aschele, A. Furlanetto, U. Cillo. - In: LIVER CANCER. - ISSN 2235-1795. - (2025). [Epub ahead of print] [10.1159/000547792]
Conversion Ability of Immunotherapy in Hepatocellular Carcinoma: Insights from the International Converse Study
M. Iavarone;E. Alimenti;V. Mazzaferro;
2025
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.
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