甲胎蛋白作为阿特珠单抗+贝伐单抗治疗肝细胞癌的潜在替代

StephenW

甲胎蛋白作为阿特珠单抗+贝伐单抗治疗肝细胞癌的潜在替代生物标志物
Andrew X Zhu 1，Farshid Dayyani 2，Chia-Jui Yen 3，任正刚 4，白玉贤 5，孟志强 6，Hongming Pan 7，Paul Dillon 8，Shivani K Mhatre 9，Vincent E Gaillard 8，Sairy Hernandez 10，Robin凯特凯利 11 ，布鲁诺桑格罗 12
隶属关系
隶属关系

    1
    嘉会国际肿瘤中心，嘉会国际医院，上海，中国。
    2
    加州大学欧文分校，奥兰治，加利福尼亚州，美国。
    3
    国立成功大学医院，国立成功大学医学院，台南，台湾。
    4
    中国上海肝癌研究所。
    5
    哈尔滨医科大学附属肿瘤医院，中国哈尔滨。
    6
    复旦大学上海肿瘤中心，上海，中国。
    7
    【作者单位】： 浙江大学医学院邵逸夫爵士医院;
    8
    F. Hoffmann-La Roche Ltd.，瑞士巴塞尔。
    9
    基因泰克公司，美国加利福尼亚州南旧金山。
    10
    基因泰克公司，美国加利福尼亚州南旧金山。
    11
    加利福尼亚大学旧金山分校，旧金山，加利福尼亚州，美国。
    12
    Clínica Universidad de Navarra and CIBEREHD，西班牙纳瓦拉潘普洛纳。

    PMID：35435967 DOI：10.1158/1078-0432.CCR-21-3275

抽象的

目的：Atezolizumab + 贝伐单抗是系统性治疗初治、不可切除的肝细胞癌 (HCC) 的新护理标准。这项探索性研究调查了治疗中的甲胎蛋白 (AFP) 反应作为联合治疗预后的潜在替代生物标志物。

实验设计：Ib 期 GO30140 研究的 A 组数据用于确定 AFP 测量和 AFP 截止值的最佳时间，以根据独立审查机构评估的实体瘤反应评估标准 (IRF-RECIST ) 1.1 版：来自无反应者的反应者和来自主要进展者的疾病控制患者。我们将这些截止值应用于来自 III 期 IMbrave150 试验的 atezolizumab + 贝伐单抗组的独立数据，以根据 (i) IRF-RECIST 1.1 的总生存期 (OS) 和无进展生存期 (PFS) 区分患者； (ii) 根据 IRF-RECIST 1.1 的最佳确认响应。

结果：我们得出的 AFP 截止值在 6 周时比基线下降 {大于或等于}75% 和 {小于或等于}10%，以分别识别反应者和疾病控制者。这些截止值在 GO30140 中具有高灵敏度和特异性。在 IMbrave150 患者中，对于{大于或等于}75% 降低 AFP 截止值，敏感性为 0.59，特异性为 0.86；对于{小于或等于}10% 增加 AFP 截止值，敏感性为 0.77，特异性为 0.44。两种 AFP 截止值均与较长的 OS 和 PFS 相关，特别是在乙型肝炎病毒病因患者中（HR <0.5；p <0.01）。

结论：开始治疗后 6 周的 AFP 反应是接受阿特珠单抗 + 贝伐单抗治疗的 HCC 患者预后的潜在替代生物标志物。

StephenW

Alpha-fetoprotein as a potential surrogate biomarker for atezolizumab + bevacizumab treatment of hepatocellular carcinoma
Andrew X Zhu  1 , Farshid Dayyani  2 , Chia-Jui Yen  3 , Zhenggang Ren  4 , Yuxian Bai  5 , Zhiqiang Meng  6 , Hongming Pan  7 , Paul Dillon  8 , Shivani K Mhatre  9 , Vincent E Gaillard  8 , Sairy Hernandez  10 , Robin Kate Kelley  11 , Bruno Sangro  12
Affiliations
Affiliations

    1
    Jiahui International Cancer Center, Jiahui International Hospital, Shanghai, China.
    2
    University of California, Irvine, Orange, CA, United States.
    3
    National Cheng Kung University Hospital, college of Medicine, National Cheng Kung University, Tainan, Taiwan.
    4
    Liver Cancer Institute, Shanghai, China.
    5
    Harbin Medical University Cancer Hospital, Harbin, China.
    6
    Fudan University Shanghai Cancer Center, Shanghai, China.
    7
    Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
    8
    F. Hoffmann-La Roche Ltd., Basel, Switzerland.
    9
    Genentech, Inc.,, South San Francisco, CA, United States.
    10
    Genentech, Inc., South San Francisco, CA, United States.
    11
    University of California, San Francisco, San Francisco, CA, United States.
    12
    Clínica Universidad de Navarra and CIBEREHD, Pamplona, Navarra, Spain.

    PMID: 35435967 DOI: 10.1158/1078-0432.CCR-21-3275

Abstract

Purpose: Atezolizumab + bevacizumab is the new standard of care for systemic treatment-naive, unresectable hepatocellular carcinoma (HCC). This exploratory study investigated on-treatment alpha-fetoprotein (AFP) response as a potential surrogate biomarker of prognosis for the combination therapy.

Experimental design: Data from Group A of the Phase Ib GO30140 study were used to identify the optimal time for AFP measurement and AFP cutoffs to differentiate patients by their best confirmed response per independent review facility-assessed Response Evaluation Criteria in Solid Tumors (IRF-RECIST) version 1.1: responders from non-responders and patients with disease control from primary progressors. We applied these cutoffs to independent data from the atezolizumab + bevacizumab arm of the Phase III IMbrave150 trial to distinguish patients based on (i) overall survival (OS) and progression-free survival (PFS) per IRF-RECIST 1.1; (ii) best confirmed response per IRF-RECIST 1.1.

Results: We derived AFP cutoffs of {greater than or equal to}75% decrease and {less than or equal to}10% increase from baseline at 6 weeks to identify responders and those who had disease control, respectively. These cutoffs had high sensitivity and specificity in GO30140. In IMbrave150 patients, sensitivity was 0.59 and specificity was 0.86 for the {greater than or equal to}75% decrease AFP cutoff; the sensitivity was 0.77 and specificity was 0.44 for the {less than or equal to}10% increase AFP cutoff. Both AFP cutoffs were associated with longer OS and PFS, particularly in patients with hepatitis B virus etiology (HR &lt;0.5; p &lt;0.01).

Conclusions: AFP response at 6 weeks after initiating treatment is a potential surrogate biomarker of prognosis for patients with HCC receiving atezolizumab + bevacizumab.

StephenW

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https://aacrjournals.org/clincan ... 964/ccr-21-3275.pdf