SP142 和 22C3 免疫组化 PD-L1 检测用于评估非小细胞肺癌患者接受阿特珠单抗疗效的比较：来自 OAK 随机临床试验的结果。

Comparison of SP142 and 22C3 Immunohistochemistry PD-L1 Assays for Clinical Efficacy of Atezolizumab in Non-Small Cell Lung Cancer: Results From the Randomized OAK Trial.

机构信息

Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI, USA.

Icahn School of Medicine, Mount Sinai, NY, USA.

出版信息

Clin Lung Cancer. 2022 Jan;23(1):21-33. doi: 10.1016/j.cllc.2021.05.007. Epub 2021 May 30.

DOI:10.1016/j.cllc.2021.05.007

PMID:34226144

Abstract

BACKGROUND

This phase III OAK trial (NCT02008227) subgroup analysis (data cutoff, January 9, 2019) evaluated the predictive value of 2 PD-L1 IHC tests (VENTANA SP142 and Dako 22C3) for benefit from atezolizumab versus docetaxel by programmed death ligand 1 (PD-L1) status in patients with previously treated metastatic non-small cell lung cancer.

METHODS

PD-L1 expression was assessed prospectively with SP142 on tumor cells (TC) and tumor-infiltrating immune cells (IC) and retrospectively with 22C3 using a tumor proportion score (TPS) based on TC membrane staining. Efficacy was assessed in the 22C3 biomarker-evaluable population (22C3-BEP) (n = 577; 47.1% of SP142-intention-to-treat population) and non-22C3-BEP (n = 648) in PD-L1 subgroups (high, low, and negative) and according to selection by 1 or both assays.

RESULTS

In the 22C3-BEP, overall survival benefits with atezolizumab versus docetaxel were observed across PD-L1 subgroups; benefits were greatest in SP142-defined PD-L1-high (TC3 or IC3: hazard ratio [HR], 0.39 [95% confidence interval (CI), 0.25-0.63]) and 22C3-defined PD-L1-high (TPS ≥ 50%: HR, 0.56 [95% CI, 0.38-0.82]) and low (TPS, 1% to < 50%: HR, 0.55 [95% CI, 0.37-0.82]) groups. Progression-free survival improved with increasing PD-L1 expression for both assays. SP142 and 22C3 assays identified overlapping and unique patient populations in PD-L1-high, positive, and negative subgroups. Overall survival and progression-free survival benefits favored atezolizumab over docetaxel in double PD-L1-positive and negative groups; patients with both SP142- and 22C3-positive tumors derived the greatest benefit.

CONCLUSIONS

Despite different scoring algorithms and differing sensitivity levels, the SP142 and 22C3 assays similarly predicted atezolizumab benefit at validated PD-L1 thresholds in patients with non-small cell lung cancer.

摘要

背景

这项 III 期 OAK 试验（NCT02008227）的亚组分析（数据截止日期为 2019 年 1 月 9 日）评估了 2 种 PD-L1 IHC 检测（VENTANA SP142 和 Dako 22C3）对先前接受过治疗的转移性非小细胞肺癌患者接受阿特珠单抗与多西他赛治疗的获益的预测价值，这些患者的程序性死亡配体 1（PD-L1）状态不同。

方法

使用 SP142 对肿瘤细胞（TC）和肿瘤浸润免疫细胞（IC）进行前瞻性评估，使用基于 TC 膜染色的肿瘤比例评分（TPS），使用 22C3 对 PD-L1 状态进行回顾性评估。在 22C3 生物标志物可评估人群（22C3-BEP）（n=577；SP142 意向治疗人群的 47.1%）和非 22C3-BEP（n=648）中，根据 PD-L1 亚组（高、低和阴性）和根据 1 种或 2 种检测的选择，评估疗效。

结果

在 22C3-BEP 中，与多西他赛相比，阿特珠单抗在所有 PD-L1 亚组中均观察到总生存期获益；在 SP142 定义的 PD-L1 高（TC3 或 IC3：风险比 [HR]，0.39 [95%置信区间（CI），0.25-0.63]）和 22C3 定义的 PD-L1 高（TPS≥50%：HR，0.56 [95%CI，0.38-0.82]）和低（TPS，1%至<50%：HR，0.55 [95%CI，0.37-0.82]）组中获益最大。对于两种检测，PD-L1 表达水平升高与无进展生存期改善相关。SP142 和 22C3 检测在 PD-L1 高、阳性和阴性亚组中确定了重叠和独特的患者人群。在双重 PD-L1 阳性和阴性组中，阿特珠单抗的总生存期和无进展生存期获益优于多西他赛；同时具有 SP142 和 22C3 阳性肿瘤的患者获益最大。