Impact of time-of-day atezolizumab plus bevacizumab combination therapy infusion for unresectable hepatocellular carcinoma: A retrospective multicenter study

IF 3.4 3区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Hepatology Research Pub Date : 2025-02-09 DOI:10.1111/hepr.14171

Atsushi Naganuma, Satoru Kakizaki, Takeshi Hatanaka, Atsushi Hiraoka, Toshifumi Tada, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hidenori Toyoda, Yuichi Koshiyama, Chikara Ogawa, Hiroki Nishikawa, Takashi Nishimura, Kazuhito Kawata, Hisashi Kosaka, Kosuke Matsui, Yutaka Yata, Hironori Tanaka, Hideko Ohama, Hidekatsu Kuroda, Tomomitsu Matono, Tomoko Aoki, Hironori Ochi, Michitaka Imai, Shinichiro Nakamura, Yuki Kanayama, Kazunari Tanaka, Fujimasa Tada, Osamu Yoshida, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Hirayuki Enomoto, Masaki Kaibori, Yoichi Hiasa, Masatoshi Kudo, Takashi Kumada, the Real-life Practice Experts for HCC (RELPEC) Study Group, and HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan)

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Abstract

Aim

This study aimed to evaluate the impact of infusion timing of time-of-day on clinical outcomes in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab combination therapy.

Methods

A retrospective analysis was conducted using data from 751 unresectable HCC patients treated with atezolizumab plus bevacizumab between September 2020 and April 2024. Patients were categorized into morning (AM; n = 351) and afternoon (PM; n = 400) groups based on infusion timing of time-of-day. Outcomes, including progression-free survival (PFS), overall survival, objective response rate, and disease control rate, were assessed using Kaplan–Meier survival analysis and Cox regression analysis.

Results

The PFS was significantly longer in the AM group (8.6 months, 95% CI 7.6–10.5) compared with the PM group (6.0 months, 95% CI 5.4–7.0; p = 0.006). In contrast, overall survival was similar between the groups (AM: 24.7 months vs. PM: 21.4 months; p = 0.99). Cox regression analysis revealed that morning infusion was an independent favorable predictor of PFS (HR 1.23, 95% CI 1.04–1.45). Additionally, the AM group demonstrated superior objective response rate and disease control rate compared with the PM group, suggesting better tumor control.

Conclusion

Morning infusion of atezolizumab plus bevacizumab is associated with improved PFS and response rates in unresectable HCC patients, highlighting the potential for optimizing treatment outcomes through circadian timing.

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阿特唑单抗加贝伐单抗联合输注治疗不可切除肝细胞癌的影响：一项回顾性多中心研究

本研究旨在评估每日输注时间对不可切除肝细胞癌（HCC）患者接受atezolizumab + bevacizumab联合治疗的临床结果的影响。方法回顾性分析2020年9月至2024年4月期间接受阿特唑单抗联合贝伐单抗治疗的751例不可切除HCC患者的数据。患者分为早晨(AM；n = 351)和下午(PM；N = 400)组。结果包括无进展生存期（PFS）、总生存期、客观有效率和疾病控制率，采用Kaplan-Meier生存分析和Cox回归分析进行评估。结果AM组PFS（8.6个月，95% CI 7.6-10.5）明显长于PM组(6.0个月，95% CI 5.4-7.0；p = 0.006)。相比之下，两组之间的总生存期相似(AM: 24.7个月vs. PM: 21.4个月；p = 0.99)。Cox回归分析显示，晨间输液是PFS的独立有利预测因子（HR 1.23, 95% CI 1.04-1.45）。AM组客观有效率和疾病控制率均优于PM组，表明AM组对肿瘤有较好的控制。结论：上午输注atezolizumab联合贝伐单抗可改善不可切除HCC患者的PFS和缓解率，突出了通过昼夜节律优化治疗结果的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hepatology Research 医学-胃肠肝病学

CiteScore

8.30

自引率

14.30%

发文量

124

审稿时长

1 months

期刊介绍： Hepatology Research (formerly International Hepatology Communications) is the official journal of the Japan Society of Hepatology, and publishes original articles, reviews and short comunications dealing with hepatology. Reviews or mini-reviews are especially welcomed from those areas within hepatology undergoing rapid changes. Short communications should contain concise definitive information.