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

Cortes, J; Lipatov, O; Im, SA; Goncalves, A; Lee, KS; Schmid, P; Tamura, K; Testa, L; Ohtani, S; Harbeck, N; Loi, S; Salgado, R; Karantza, V; Mejia, J; Cristescu, R; Loboda, A; Nebozhyn, M; Jelinic, P; Huang, L; Winer, EP

Author(s): Cortes, J; Lipatov, O; Im, SA; Goncalves, A; Lee, KS; Schmid, P; Tamura, K; Testa, L; Ohtani, S; Harbeck, N; Loi, S; Salgado, R; Karantza, V; Mejia, J; Cristescu, R; Loboda, A; Nebozhyn, M; Jelinic, P; Huang, L; Winer, EP;
Details: Publication Year 2025-10-02,Volume 11,Issue #1,Page 109
Journal Title: NPJ Breast Cancer
Publication Type: Research article
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(inf)GEP), 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(inf)GEP. Associations were also identified between Tcell(inf)GEP 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(inf)GEP, and TMB with clinical outcomes in patients with metastatic TNBC receiving pembrolizumab. ClinicalTrials.gov Identifier: NCT02555657 (date of registration: September 18, 2015).
Publisher: Springer Nature
Department(s): Medical Oncology; Laboratory Research
Publisher's Version: https://doi.org/10.1038/s41523-025-00814-y
Open Access at Publisher's Site: https://doi.org/10.1038/s41523-025-00814-y
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-11-06 11:44:59

Last Modified: 2025-11-06 11:45:06