α‐FAtE: A new predictive score of response to atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma
Authors: Rossari Federico , Tada Toshifumi , Suda Goki , Shimose Shigeo , Kudo Masatoshi , Yoo Changhoon , Cheon Jaekyung , Finkelmeier Fabian , Lim Ho Yeong , Presa José , Masi Gianluca , Bergamo Francesca , Amadeo Elisabeth , Vitiello Francesco , Kumada Takashi , Sakamoto Naoya , Iwamoto Hideki , Aoki Tomoko , Chon Hong Jae , Himmelsbach Vera , Iavarone Massimo , Cabibbo Giuseppe , Montes Margarida , Foschi Francesco Giuseppe , Vivaldi Caterina , Soldà Caterina , Sho Takuya , Niizeki Takashi , Nishida Naoshi , Steup Christoph , Hirooka Masashi , Kariyama Kazuya , Tani Joji , Atsukawa Masanori , Takaguchi Koichi , Itobayashi Ei , Fukunishi Shinya , Tsuji Kunihiko , Ishikawa Toru , Tajiri Kazuto , Ochi Hironori , Yasuda Satoshi , Toyoda Hidenori , Ogawa Chikara , Nishimura Takashi , Hatanaka Takeshi , Kakizaki Satoru , Shimada Noritomo , Kawata Kazuhito , Hiraoka Atsushi , Tada Fujimasa , Ohama Hideko , Nouso Kazuhiro , Morishita Asahiro , Tsutsui Akemi , Nagano Takuya , Itokawa Norio , Okubo Tomomi , Imai Michitaka , Kosaka Hisashi , Naganuma Atsushi , Koizumi Yohei , Nakamura Shinichiro , Kaibori Masaki , Iijima Hiroko , Hiasa Yoichi , Persano Mara , Burgio Valentina , Piscaglia Fabio , Scartozzi Mario , Cascinu Stefano , Casadei‐Gardini Andrea , Rimini Margherita 
Published: November 2023

Atezolizumab plus bevacizumab (AB) and lenvatinib can be alternatively used as first‐line systemic treatment of unresectable hepatocellular carcinoma (HCC). However, no direct comparison of the two regimens has been performed in randomized clinical trials, making the identification of baseline differential predictors of response of major relevance to tailor the best therapeutic option to each patient. Baseline clinical and laboratory characteristics of real‐world AB‐treated HCC patients were analyzed in uni‐ and multivariate analyses to find potential prognostic factors of overall survival (OS). Significant variables were incorporated in a composite score (α‐FAtE) and it was tested for specificity and sensitivity in receiver operating characteristic (ROC) curve and in multivariate analysis for OS. The score was applied in uni‐ and multivariate analyses for OS of a comparable lenvatinib‐treated HCC population. Finally, comparison between treatments was performed in patients with low and high α‐FAtE scores and predictivity estimated by interaction analysis. Time‐to‐progression (TTP) was a secondary endpoint. OS of AB‐treated HCC patients was statistically longer in those with α‐fetoprotein <400 ng/mL (HR 0.62, p = .0407), alkaline phosphatase (ALP) <125 IU/L (HR 0.52, p = .0189) and eosinophil count ≥70/μL (HR 0.46, p = .0013). The α‐FAtE score was generated by the sum of single points attributed to each variable among the above reported. In ROC curve analysis, superior sensitivity and specificity were achieved by the score compared to individual variables (AUC 0.794, p < .02). Patients with high score had longer OS (HR 0.44, p = .0009) and TTP (HR 0.34, p < .0001) compared to low score if treated with AB, but not with lenvatinib. Overall, AB was superior to lenvatinib in high score patients (HR 0.55, p = .0043) and inferior in low score ones (HR 1.75, p = .0227). At interaction test, low α‐FAtE score resulted as negative predictive factor of response to AB (p = .0004). In conclusion, α‐FAtE is a novel prognostic and predictive score of response to first‐line AB for HCC patients that, if validated in prospective studies, could drive therapeutic choice between lenvatinib and AB.