Association Between Biomarkers and Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Metastatic Triple-Negative Breast Cancer: KEYNOTE-086 Exploratory Analysis
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
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

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