Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer.
Adult
Aged
Antibodies, Monoclonal, Humanized
/ therapeutic use
Antigen Presentation
/ genetics
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
B7-H1 Antigen
/ metabolism
Breast Neoplasms
/ drug therapy
Cytokines
/ blood
Drug Resistance, Neoplasm
/ genetics
Estrogens
/ metabolism
Female
Furans
/ therapeutic use
Gene Expression Profiling
Genetic Heterogeneity
Genome, Human
/ genetics
Genomics
Humans
Immune Checkpoint Inhibitors
/ therapeutic use
Ketones
/ therapeutic use
Lymphocytes, Tumor-Infiltrating
/ immunology
Male
Middle Aged
Mutation
Neoplasm Metastasis
Receptors, Estrogen
/ metabolism
Receptors, Progesterone
/ metabolism
Signal Transduction
/ genetics
Survival Rate
Treatment Outcome
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 09 2021
21 09 2021
Historique:
received:
12
02
2021
accepted:
31
08
2021
entrez:
22
9
2021
pubmed:
23
9
2021
medline:
21
10
2021
Statut:
epublish
Résumé
Immune checkpoint inhibitors (ICIs) have minimal therapeutic effect in hormone receptor-positive (HR+ ) breast cancer. We present final overall survival (OS) results (n = 88) from a randomized phase 2 trial of eribulin ± pembrolizumab for patients with metastatic HR+ breast cancer, computationally dissect genomic and/or transcriptomic data from pre-treatment tumors (n = 52) for molecular associations with efficacy, and identify cytokine changes differentiating response and ICI-related toxicity (n = 58). Despite no improvement in OS with combination therapy (hazard ratio 0.95, 95% CI 0.59-1.55, p = 0.84), immune infiltration and antigen presentation distinguished responding tumors, while tumor heterogeneity and estrogen signaling independently associated with resistance. Moreover, patients with ICI-related toxicity had lower levels of immunoregulatory cytokines. Broadly, we establish a framework for ICI response in HR+ breast cancer that warrants diagnostic and therapeutic validation. ClinicalTrials.gov Registration: NCT03051659.
Identifiants
pubmed: 34548479
doi: 10.1038/s41467-021-25769-z
pii: 10.1038/s41467-021-25769-z
pmc: PMC8455578
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
B7-H1 Antigen
0
CD274 protein, human
0
Cytokines
0
Estrogens
0
Furans
0
Immune Checkpoint Inhibitors
0
Ketones
0
Receptors, Estrogen
0
Receptors, Progesterone
0
pembrolizumab
DPT0O3T46P
eribulin
LR24G6354G
Banques de données
ClinicalTrials.gov
['NCT03051659']
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
5563Subventions
Organisme : NCI NIH HHS
ID : T32 CA009172
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008313
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG002295
Pays : United States
Informations de copyright
© 2021. The Author(s).
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