甲胎蛋白作为 Atezolizumab + Bevacizumab 治疗肝细胞癌的潜在替代

StephenW

甲胎蛋白作为 Atezolizumab + Bevacizumab 治疗肝细胞癌的潜在替代生物标志物
安德鲁·X·朱；
法尔希德·戴亚尼；
贾瑞燕；
任正刚；
白玉贤；
孟志强；
潘红明；
保罗狄龙；
Shivani K. Mhatre；
文森特·E·盖拉德；
赛里·埃尔南德斯；
罗宾·凯特·凯利；
布鲁诺·桑格罗

临床癌症研究 (2022) 28 (16): 3537–3545。
https://doi.org/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：

来自 Ib 期 GO30140 研究 A 组的数据用于确定 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 RECIST (IRF-RECIST) 1.1 版的最佳确认反应来区分患者：来自无反应者的反应者和疾病控制从主要进展者的患者。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) 和 (ii) 最佳来区分患者根据 IRF-RECIST 1.1 确认响应。
结果：

我们得出在 6 周时从基线下降 ≥ 75% 和增加 ≤ 10% 的 AFP 截止值，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，AFP 临界值降低 ≥75% 的敏感性为 0.59，特异性为 0.86；对于 ≤10% 的 AFP 临界值增加，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;
Farshid Dayyani;
Chia-Jui Yen;
Zhenggang Ren;
Yuxian Bai;
Zhiqiang Meng;
Hongming Pan;
Paul Dillon;
Shivani K. Mhatre;
Vincent E. Gaillard;
Sairy Hernandez;
Robin Kate Kelley;
Bruno Sangro

Clin Cancer Res (2022) 28 (16): 3537–3545.
https://doi.org/10.1158/1078-0432.CCR-21-3275

Abstract
Purpose:

Atezolizumab + bevacizumab is the new standard of care for systemic treatment-naïve, 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 RECIST (IRF-RECIST) version 1.1: responders from nonresponders 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 and (ii) best confirmed response per IRF-RECIST 1.1.
Results:

We derived AFP cutoffs of ≥75% decrease and ≤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 ≥75% decrease AFP cutoff; the sensitivity was 0.77 and specificity was 0.44 for the ≤10% increase AFP cutoff. Both AFP cutoffs were associated with longer OS and PFS, particularly in patients with hepatitis B virus etiology (HR < 0.5; P < 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

https://aacrjournals.org/clincan ... 908/ccr-21-3275.pdf