在两个队列的II期KEYNOTE-086研究（ClinicalTrials.gov识别号：NCT02447003）中，第一线和第二线或更后期的帕博利珠单药治疗在转移性三阴性乳腺癌（mTNBC; N = 254）中展示了抗肿瘤活性。这项探索性分析评估了预定分子生物标志物与临床结果的关联。队列A纳入PD-L1状态不确定的进行一种或多种转移性疾病系统治疗后出现疾病进展的患者；队列B纳入先前未经治疗的PD-L1阳性（联合阳性评分[CPS]≥1）转移性疾病的患者。评估以下生物标志物作为连续变量与临床结果（客观缓解率[ORR]，无进展生存期[PFS]和总生存期[OS]）之间的关联：PD-L1 CPS（免疫组织化学），细胞群集分化8号（CD8;免疫组织化学），基质肿瘤浸润淋巴细胞（sTIL;苏木精和伊红染色），肿瘤突变负荷（TMB;全外显子组测序[WES]），同源重组缺陷-失去杂合子，突变签名3（WES），突变签名2（载脂蛋白B mRNA编辑催化酶样; WES），T细胞炎症基因表达谱（TcellinfGEP;RNA测序）和10个非TcellinfGEP标志（RNA测序）；使用Wald检验P值进行计算，并预先指定显着性为α=0.05。在联合队列（A和B）中，PD-L1（P = .040），CD8（P <.001），sTIL（P = .012），TMB（P = .007）和TcellinfGEP（P = .011）与ORR 显着关联；CD8（P <.001），TMB（P = .034），Signature 3（P = .009）和TcellinfGEP（P = .002）与PFS显着相关；CD8（P <.001），sTIL（P = .004），TMB（P = .025）和TcellinfGEP（P = .001）与OS显着相关。在调整了TcellinfGEP之后，没有非TcellinfGEP标志与帕博利珠治疗的结果有关。在这个来自KEYNOTE-086的探索性生物标志物分析中，基线肿瘤PD-L1，CD8，sTIL，TMB和TcellinfGEP与帕博利珠的临床结果显着相关，可以帮助识别对帕博利珠单药治疗最有可能作出反应的mTNBC患者。

In the two-cohort phase II KEYNOTE-086 study (ClinicalTrials.gov identifier: NCT02447003), first-line and second-line or later pembrolizumab monotherapy demonstrated antitumor activity in metastatic triple-negative breast cancer (mTNBC; N = 254). This exploratory analysis evaluates the association between prespecified molecular biomarkers and clinical outcomes.Cohort A enrolled patients with disease progression after one or more systemic therapies for metastatic disease irrespective of PD-L1 status; Cohort B enrolled patients with previously untreated PD-L1-positive (combined positive score [CPS] ≥ 1) metastatic disease. The association between the following biomarkers as continuous variables and clinical outcomes (objective response rate [ORR], progression-free survival [PFS], and overall survival [OS]) was evaluated: PD-L1 CPS (immunohistochemistry), cluster of differentiation 8 (CD8; immunohistochemistry), stromal tumor-infiltrating lymphocyte (sTIL; hematoxylin and eosin staining), tumor mutational burden (TMB; whole-exome sequencing [WES]), homologous recombination deficiency-loss of heterozygosity, mutational signature 3 (WES), mutational signature 2 (apolipoprotein B mRNA editing catalytic polypeptide-like; WES), T-cell-inflamed gene expression profile (TcellinfGEP; RNA sequencing), and 10 non-TcellinfGEP signatures (RNA sequencing); Wald test P values were calculated, and significance was prespecified at α = 0.05.In the combined cohorts (A and B), PD-L1 (P = .040), CD8 (P < .001), sTILs (P = .012), TMB (P = .007), and TcellinfGEP (P = .011) were significantly associated with ORR; CD8 (P < .001), TMB (P = .034), Signature 3 (P = .009), and TcellinfGEP (P = .002) with PFS; and CD8 (P < .001), sTILs (P = .004), TMB (P = .025), and TcellinfGEP (P = .001) with OS. None of the non-TcellinfGEP signatures were associated with outcomes of pembrolizumab after adjusting for the TcellinfGEP.In this exploratory biomarker analysis from KEYNOTE-086, baseline tumor PD-L1, CD8, sTILs, TMB, and TcellinfGEP were associated with improved clinical outcomes of pembrolizumab and may help identify patients with mTNBC who are most likely to respond to pembrolizumab monotherapy.