Department of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China.
State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.
Front Immunol. 2023 Mar 6;14:1060308. doi: 10.3389/fimmu.2023.1060308. eCollection 2023.
Inhibitors of programmed cell death 1 (PD-1)/programmed cell death ligand 1(PD-L1) checkpoint have been approved for metastatic triple negative breast cancer (mTNBC) in patients positive for PD-L1 expression. Negative results from the recent phase III trials (IMPassion131 and IMPassion132) have raises questions on the efficacy of PD-1/PD-L1 checkpoint inhibitors and the predictive value of PD-L1 expression. Here we attempt to systematically analyze the biomarker value of PD-L1 expression for predicting the response of PD-1/PD-L1 checkpoint inhibitors in mTNBC.
PubMed database was searched until Dec 2021 for studies evaluating PD-1/PD-L1 checkpoint inhibitors plus/minus chemotherapy in mTNBC. Outcome of interest included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Review Manager (RevMan) version 5.4. was used for data-analysis.
In total, 20 clinical trials comprising 3962 mTNBC patients (ICT: 2665 (67%); CT: 1297 (33%) were included in this study. Overall ORR was 22% (95%CI, 14-30%) and significant improvement was observed for PD-L1+ patients (ORR 1.78 [95%CI, 1.45-2.19], p<0.00001) as compared to PD-L1- cohort. Pooled outcome also indicated a significant 1-year PFS and 2-year OS advantage for patients with PD-L1 expression (1-year PFS: ORR 1.39 [95%CI, 1.04-1.85], p=0.02; I 0%; 2-year OS: (ORR 2.47 [95%CI, 1.30-4.69], p=0.006; I 63%). Subgroup analysis indicated that PD-L1 expression can successfully predict tumor response and 2-year OS benefit in mTNBC patients regardless of the type of investigating agent, line of treatment administration, and to some extent the type of treatment. Biomarker ability of PD-L1 expression to predict 1-year PFS was slightly better with pembrolizumab (p=0.09) than atezolizumab (p=0.18), and significantly better when treatment was administered in the first-line setting (OR 1.38 [95%CI, 1.02-1.87], p=0.04) and chemotherapy was added (OR 1.38 [95%CI, 1.02-1.86], p=0.03). Immune-related toxicity of any grade and grade≥3 was 39% (95%CI, 26%-52%) and 10% (95%CI, 8%-13%), respectively.
PD-L1 expression can predict objective response rate and 2-year OS in mTNBC patients receiving PD-1/PD-L1 checkpoint inhibitors. One-year PFS is also predicted in selected patients. PD-L1 expression can be a useful biomarker of efficacy of PD-1/PD-L1 checkpoint inhibitors in mTNBC.
程序性细胞死亡蛋白 1（PD-1）/程序性细胞死亡配体 1（PD-L1）检查点抑制剂已被批准用于 PD-L1 表达阳性的转移性三阴性乳腺癌（mTNBC）患者。最近的 III 期试验（IMPassion131 和 IMPassion132）的阴性结果引发了人们对 PD-1/PD-L1 检查点抑制剂疗效和 PD-L1 表达预测价值的质疑。在这里，我们试图系统地分析 PD-L1 表达作为预测 mTNBC 中 PD-1/PD-L1 检查点抑制剂反应的生物标志物的价值。
检索 PubMed 数据库，直到 2021 年 12 月，以评估 PD-1/PD-L1 检查点抑制剂联合/不联合化疗治疗 mTNBC 的研究。感兴趣的结果包括客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。使用 Review Manager（RevMan）版本 5.4 进行数据分析。
共纳入 20 项临床试验，包括 3962 例 mTNBC 患者（ICT：2665 例[67%]；CT：1297 例[33%]）。总体 ORR 为 22%（95%CI，14-30%），PD-L1+患者的缓解率显著提高（ORR 1.78[95%CI，1.45-2.19]，p<0.00001）。荟萃分析结果还表明，PD-L1 表达的患者 PFS 和 OS 获益具有统计学意义（1 年 PFS：ORR 1.39[95%CI，1.04-1.85]，p=0.02；I 0%；2 年 OS：ORR 2.47[95%CI，1.30-4.69]，p=0.006；I 63%）。亚组分析表明，无论检查点抑制剂的类型、治疗线数以及在某种程度上治疗类型如何，PD-L1 表达都可以成功预测 mTNBC 患者的肿瘤反应和 2 年 OS 获益。PD-L1 表达预测 1 年 PFS 的能力在使用 pembrolizumab 时略优于 atezolizumab（p=0.09），而在一线治疗和添加化疗时则具有显著优势（OR 1.38[95%CI，1.02-1.87]，p=0.04）。任何等级和≥3 级的免疫相关毒性分别为 39%（95%CI，26%-52%）和 10%（95%CI，8%-13%）。
PD-L1 表达可预测 mTNBC 患者接受 PD-1/PD-L1 检查点抑制剂治疗的客观缓解率和 2 年 OS。在选定的患者中也可以预测 1 年 PFS。PD-L1 表达可以作为 mTNBC 中 PD-1/PD-L1 检查点抑制剂疗效的有用生物标志物。
