Association Between Biomarkers and Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Metastatic Triple-Negative Breast Cancer: KEYNOTE-086 Exploratory Analysis
- Author(s)
- Loi, S; Salgado, R; Schmid, P; Cortes, J; Cescon, DW; Winer, EP; Toppmeyer, DL; Rugo, HS; De Laurentiis, M; Nanda, R; Iwata, H; Awada, A; Tan, AR; Sun, Y; Karantza, V; Wang, A; Huang, L; Saadatpour, A; Cristescu, R; Yearley, J; Lunceford, J; Jelinic, P; Adams, S;
- Journal Title
- JCO Precision Oncology
- Publication Type
- Research article
- Abstract
- PURPOSE: 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. METHODS: 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 (Tcell(inf)GEP; RNA sequencing), and 10 non-Tcell(inf)GEP signatures (RNA sequencing); Wald test P values were calculated, and significance was prespecified at alpha = 0.05. RESULTS: In the combined cohorts (A and B), PD-L1 (P = .040), CD8 (P < .001), sTILs (P = .012), TMB (P = .007), and Tcell(inf)GEP (P = .011) were significantly associated with ORR; CD8 (P < .001), TMB (P = .034), Signature 3 (P = .009), and Tcell(inf)GEP (P = .002) with PFS; and CD8 (P < .001), sTILs (P = .004), TMB (P = .025), and Tcell(inf)GEP (P = .001) with OS. None of the non-Tcell(inf)GEP signatures were associated with outcomes of pembrolizumab after adjusting for the Tcell(inf)GEP. CONCLUSION: In this exploratory biomarker analysis from KEYNOTE-086, baseline tumor PD-L1, CD8, sTILs, TMB, and Tcell(inf)GEP were associated with improved clinical outcomes of pembrolizumab and may help identify patients with mTNBC who are most likely to respond to pembrolizumab monotherapy.
- Publisher
- American Society of Clinical Oncology
- Keywords
- Humans; B7-H1 Antigen/genetics; *Triple Negative Breast Neoplasms/drug therapy/genetics; *Antineoplastic Agents, Immunological/therapeutic use; Biomarkers, Tumor/genetics
- Department(s)
- Medical Oncology
- PubMed ID
- 37099733
- Publisher's Version
- https://doi.org/10.1200/PO.22.00317
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-07-27 08:03:05
Last Modified: 2023-07-27 08:03:33