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