Association of potential biomarkers with clinical outcomes in metastatic triple-negative breast cancer treated with pembrolizumab or chemotherapy
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<sub>inf</sub>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<sub>inf</sub>GEP. Associations were also identified between Tcell<sub>inf</sub>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<sub>inf</sub>GEP, and TMB with clinical outcomes in patients with metastatic TNBC receiving pembrolizumab. ClinicalTrials.gov Identifier: NCT02555657 (date of registration: September 18, 2015).
Authors
- Anthony Gonçalvès (ORCID: https://orcid.org/0000-0001-7570-7439)
- Sherene Loi (ORCID: https://orcid.org/0000-0001-6137-9171)
- Roberto Salgado (ORCID: https://orcid.org/0000-0002-1110-3801)
- Petar Jelinic (ORCID: https://orcid.org/0000-0002-7361-5239)
- Nadia Harbeck (ORCID: https://orcid.org/0000-0002-9744-7372)
- Laura Testa (ORCID: https://orcid.org/0000-0001-6080-7429)
- Peter Schmid (ORCID: https://orcid.org/0000-0002-2510-3941)
- Keun Seok Lee (ORCID: https://orcid.org/0000-0001-5575-836X)
- Oleg Lipatov (ORCID: https://orcid.org/0000-0002-8867-504X)
- Michael Nebozhyn (ORCID: https://orcid.org/0000-0001-8835-7714)
- Lingkang Huang
- Răzvan Cristescu (ORCID: https://orcid.org/0000-0002-9978-0339)
- Seock‐Ah Im (ORCID: https://orcid.org/0000-0002-5396-6533)
- Kenji Tamura (ORCID: https://orcid.org/0000-0002-3514-9927)
- Eric P. Winer (ORCID: https://orcid.org/0000-0002-8819-1723)
- Andrey Loboda
- Vassiliki Karantza (ORCID: https://orcid.org/0000-0003-4017-7858)
- Jaime Mejia (ORCID: https://orcid.org/0000-0002-1315-6878)
- Javier Cortes
- Shoichiro Ohtani
Institutions
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- The University of Melbourne (AU)
- Queen Mary University of London (GB)
- Peter MacCallum Cancer Centre (AU)
- Yale Cancer Center (US)
- Seoul National University Hospital (KR)
- Instituto do Câncer do Estado de São Paulo (BR)
- Hiroshima City Asa Citizens Hospital (JP)
- National Cancer Center (KR)
- Republican Oncological Clinical Dispensary (RU)
- Centre de Recherche en Cancérologie de Marseille (FR)
- Institut Paoli-Calmettes (FR)
- Tokyo National Hospital (JP)
- Ludwig-Maximilians-Universität München (DE)
- Universidad Europea de Madrid (ES)
Publication Details
- Journal
- npj Breast Cancer
- Published
- 2025-10-02
- DOI
- https://doi.org/10.1038/s41523-025-00814-y
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 0.00