Chuma Makoto, Uojima Haruki, Hattori Nobuhiro, Arase Yoshitaka, Fukushima Taito, Hirose Shunji, Kobayashi Satoshi, Ueno Makoto, Tezuka Shun, Iwasaki Shuichiro, Wada Naohisa, Kubota Kousuke, Tsuruya Kota, Shimma Yoshimasa, Hiroki Ikeda, Takuya Ehira, Tokoro Chikako, Iwase Shigeru, Miura Yuki, Moriya Satoshi, Watanabe Tsunamasa, Hidaka Hisashi, Morimoto Manabu, Numata Kazushi, Kusano Chika, Kagawa Tatehiro, Maeda Shin
Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan.
Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
Hepatol Res. 2022 Mar;52(3):269-280. doi: 10.1111/hepr.13732. Epub 2021 Nov 30.
To assess the impact of clinical factors on the safety and efficacy of atezolizumab plus bevacizumab (ATZ + BV) treatment in patients with unresectable hepatocellular carcinoma (u-HCC).
Ninety-four u-HCC patients who were treated with ATZ + BV at multiple centers were enrolled. We defined Child-Pugh (CP)-A patients who received ATZ + BV treatment as a first line therapy as the 'meets the broad sense of the IMbrave150 criteria' group (B-IMbrave150-in, n = 46), and patients who received ATZ + BV treatment as a later line therapy or CP-B patients (regardless of whether ATZ + BV was a first line or later line therapy) as the B-IMbrave150-out group (n = 48). Patients were retrospectively analyzed for adverse events (AEs) and treatment outcomes according to their clinical characteristics, including neutrophil lymphocyte ratio (NLR) at baseline.
The overall incidence of AEs was 87.2% (82/94 patients). The frequency of interruption of ATZ + BV treatment due to fatigue was higher in CP-B than CP-A patients (p = 0.030). Objective response (OR) rates of the B-IMbrave150-in group (28.3%, 39.1%) were significantly higher than those of the B-IMbrave150-out group (8.3%, 18.8%; p = 0.0157, 0.0401) using Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST, respectively. In multivariate analysis, NLR (hazard ratio (HR), 4.591; p = 0.0160) and B-IMbrave150 criteria (HR, 4.108; p = 0.0261) were independent factors associated with the OR of ATZ + BV treatment using RECIST.
In real-world practice, ATZ + BV treatment might offer significant benefits in patients who meet B-IMbrave150 criteria or have low NLR.
评估临床因素对阿替利珠单抗联合贝伐珠单抗（ATZ + BV）治疗不可切除肝细胞癌（u-HCC）患者安全性和疗效的影响。
纳入94例在多个中心接受ATZ + BV治疗的u-HCC患者。我们将接受ATZ + BV一线治疗的Child-Pugh（CP）-A患者定义为“符合广义IMbrave150标准”组（B-IMbrave150-in，n = 46），将接受ATZ + BV二线或更后线治疗的患者或CP-B患者（无论ATZ + BV是一线还是二线治疗）定义为B-IMbrave150-out组（n = 48）。根据患者的临床特征，包括基线中性粒细胞淋巴细胞比值（NLR），对不良事件（AE）和治疗结果进行回顾性分析。
AE的总发生率为87.2%（82/94例患者）。CP-B患者因疲劳导致ATZ + BV治疗中断的频率高于CP-A患者（p = 0.030）。分别使用实体瘤疗效评价标准（RECIST）和改良RECIST，B-IMbrave150-in组的客观缓解（OR）率（28.3%，39.1%）显著高于B-IMbrave150-out组（8.3%，18.8%；p = 0.0157，0.0401）。在多因素分析中，使用RECIST时，NLR（风险比（HR），4.591；p = 0.0160）和B-IMbrave150标准（HR，4.108；p = 0.0261）是与ATZ + BV治疗OR相关的独立因素。
在实际临床实践中，ATZ + BV治疗可能对符合B-IMbrave150标准或NLR较低的患者有显著益处。
