Association of potential biomarkers with clinical outcomes in metastatic triple-negative breast cancer treated with pembrolizumab or chemotherapy.

IF 7.6 2区医学 Q1 ONCOLOGY

NPJ Breast Cancer Pub Date : 2025-10-02 DOI:10.1038/s41523-025-00814-y

Javier Cortes, Oleg Lipatov, Seock-Ah Im, Anthony Goncalves, Keun Seok Lee, Peter Schmid, Kenji Tamura, Laura Testa, Shoichiro Ohtani, Nadia Harbeck, Sherene Loi, Roberto Salgado, Vassiliki Karantza, Jaime Mejia, Razvan Cristescu, Andrey Loboda, Michael Nebozhyn, Petar Jelinic, Lingkang Huang, Eric P Winer

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引用次数: 0

Abstract

In the randomized, phase 3 KEYNOTE-119 study, overall survival (OS) was not significantly improved with pembrolizumab 200 mg Q3W versus investigator's choice of chemotherapy in participants with previously treated metastatic TNBC. In this exploratory analysis, we evaluated associations of tumor-infiltrating lymphocytes (TILs), T-cell‒inflamed gene expression profile (Tcell_infGEP), BRCA1/BRCA2 mutation (BRCAm) status, homologous recombination deficiency (HRD) status, and tumor mutational burden (TMB) with clinical outcomes. TIL level was associated with improved objective response rate (ORR), progression-free survival (PFS), and OS with pembrolizumab but not with chemotherapy or after adjusting for Tcell_infGEP. Associations were also identified between Tcell_infGEP and improved ORR, PFS, and OS with pembrolizumab. Participants with TMB ≥ 10 mut/Mb showed a trend toward increased benefit with pembrolizumab versus chemotherapy. No association was seen between BRCAm/HRD status and treatment response. These findings suggest a positive association between TILs, Tcell_infGEP, and TMB with clinical outcomes in patients with metastatic TNBC receiving pembrolizumab. ClinicalTrials.gov Identifier: NCT02555657 (date of registration: September 18, 2015).

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pembrolizumab或化疗治疗转移性三阴性乳腺癌的潜在生物标志物与临床结果的关联

在随机3期KEYNOTE-119研究中，与研究者选择的化疗相比，pembrolizumab 200mg Q3W对既往治疗过的转移性TNBC患者的总生存期（OS）没有显着改善。在这项探索性分析中，我们评估了肿瘤浸润淋巴细胞（TILs）、t细胞炎症基因表达谱（TcellinfGEP）、BRCA1/BRCA2突变（BRCAm）状态、同源重组缺陷（HRD）状态和肿瘤突变负担（TMB）与临床结果的关系。使用派姆单抗时，TIL水平与改善的客观缓解率（ORR）、无进展生存期（PFS）和OS相关，但与化疗或调整TcellinfGEP后无关。TcellinfGEP与pembrolizumab改善的ORR、PFS和OS之间也存在关联。TMB≥10 mut/Mb的患者与化疗相比，派姆单抗的获益增加。BRCAm/HRD状态与治疗反应之间未见关联。这些发现表明，在接受派姆单抗治疗的转移性TNBC患者中，TILs、TcellinfGEP和TMB与临床结果呈正相关。ClinicalTrials.gov标识符：NCT02555657（注册日期：2015年9月18日）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

NPJ Breast Cancer Medicine-Pharmacology (medical)

CiteScore

10.10

自引率

1.70%

发文量

122

审稿时长

9 weeks

期刊介绍： npj Breast Cancer publishes original research articles, reviews, brief correspondence, meeting reports, editorial summaries and hypothesis generating observations which could be unexplained or preliminary findings from experiments, novel ideas, or the framing of new questions that need to be solved. Featured topics of the journal include imaging, immunotherapy, molecular classification of disease, mechanism-based therapies largely targeting signal transduction pathways, carcinogenesis including hereditary susceptibility and molecular epidemiology, survivorship issues including long-term toxicities of treatment and secondary neoplasm occurrence, the biophysics of cancer, mechanisms of metastasis and their perturbation, and studies of the tumor microenvironment.