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

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.; 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.; Solda, C.; Bergamo, F.; Pinato, D. J.; Pelizzaro, F.; Foschi, F. G.; Secomandi, A.; Verderame, F.; Bronte, E.; Martinelli, E.; Marino, D.; Grasselli, S.; Olivani, A.; Brunetto, M. R.; Damone, F.; Mega, A.; Marzi, L.; Tamburini, E.; Ramundo, M.; Quintarelli, Federico; Daniele, B.; Giannini, E. G.; 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, M. L.; Farella, N.; Rendina, M.; Grassi, T.; Rodriquenz, M. G.; Maiello, E.; Presa, J.; Pinho, I.; Hiasa, Y.; Hirooka, M.; Chen, J.; Arrichiello, G.; Aschele, C.; Furlanetto, A.; Cillo, U.

doi:10.1159/000547792

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.