Optimizing bevacizumab exposure in atezolizumab-based therapy for unresectable hepatocellular carcinoma: A nationwide real-world study.
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Aoe Kaho, Tada Toshifumi, Hiraoka Atsushi, Matono Tomomitsu, Hirooka Masashi, Kariyama Kazuya, Tani Joji, Atsukawa Masanori, Takaguchi Koichi, Itobayashi Ei, Nishimura Takashi, Tsuji Kunihiko, Ishikawa Toru, Tajiri Kazuto, Tanaka Hironori, Toyoda Hidenori, Ogawa Chikara, Hatanaka Takeshi, Kakizaki Satoru, Kawata Kazuhito, Atsushi Naganuma, Kosaka Hisashi, Kuroda Hidekatsu, Yata Yutaka, Nishikawa Hiroki, Imai Michitaka, Aoki Tomoko, Ochi Hironori, Tamai Hideyuki, Komatsu Shohei, Matsuura Takanori, Ueda Yoshihide, Kim Soo Ki, Ohama Hideko, Tada Fujimasa, Nakamura Shinichiro, Nakamura Yoshiko, Yoshida Osamu, Nouso Kazuhiro, Morishita Asahiro, Itokawa Norio, Okubo Tomomi, Arai Taeang, Tsutsui Akemi, Nagano Takuya, Fukunishi Shinya, Tanaka Kazunari, Koshiyama Yuichi, Kanayama Yuki, Noritake Hidenao, Enomoto Hirayuki, Matsui Kosuke, Kaibori Masaki, Okamura Jumpei, Fukumoto Takumi, Hiasa Yoichi, Kudo Masatoshi, Kumada Takashi, RELPEC Group and HCC 48 Group
Аннотация
APPROACH AND RESULTS: This retrospective study included 1507 patients with unresectable HCC treated with atezolizumab plus bevacizumab at 30 Japanese institutions. BBI was the ratio of actual to standard dose per BSA. Restricted cubic spline analyses identified the optimal BBI range. Outcomes were compared among BBI groups. Spline analysis revealed a nonlinear association between BBI and overall survival (OS), with an optimal BBI range of 106%-121%. Accordingly, the patients were classified into under (n=924), target (n=522), and over (n=61) groups. The median progression-free survival was significantly longer in the target group than in the nontarget group (10.3 vs. 6.5 mo, p <0.001), and the median OS was prolonged (24.9 vs. 19.2 mo, p =0.008). Multivariable analysis demonstrated that the target BBI group was independently associated with improved progression-free survival (HR, 0.807; 95% CI: 0.715-0.910; p <0.001) and OS (HR, 0.850; 95% CI: 0.733-0.985; p =0.031). The objective response rate was significantly higher in the Target group ( p =0.023), while treatment-related adverse event rates were comparable across the BBI groups, with no significant differences in proteinuria, hypertension, or other toxicities.
CONCLUSIONS: BSA-adjusted bevacizumab dosing was associated with improved efficacy without increased toxicity in patients with unresectable HCC treated with atezolizumab plus bevacizumab.