Neoadjuvant sunitinib plus exemestane in post-menopausal women with hormone receptor-positive/HER2-negative early-stage breast cancer (SUT_EXE-08): a phase I/II trial.
Humans
Female
Sunitinib
/ therapeutic use
Breast Neoplasms
/ drug therapy
Aged
Androstadienes
/ administration & dosage
Postmenopause
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Middle Aged
Receptor, ErbB-2
/ metabolism
Neoadjuvant Therapy
Receptors, Estrogen
/ metabolism
Neoplasm Staging
Receptors, Progesterone
/ metabolism
Aged, 80 and over
Treatment Outcome
Biomarkers, Tumor
/ metabolism
Antiangiogenic therapy
Breast cancer
Exemestane
Neoadjuvant endocrine therapy
PAM50
Sunitinib
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
09 10 2024
09 10 2024
Historique:
received:
15
06
2024
accepted:
04
09
2024
medline:
10
10
2024
pubmed:
10
10
2024
entrez:
9
10
2024
Statut:
epublish
Résumé
Neoadjuvant endocrine therapy (NET) for hormone receptor-positive (HR+) breast cancer might be as effective as chemotherapy, with a better toxicity profile. Blocking a crucial process such as angiogenesis with sunitinib may have a synergistic effect with NET. We aimed to assess the efficacy and safety of neoadjuvant sunitinib plus exemestane in early-stage HR+/HER2-negative breast cancer. In this phase I/II study, postmenopausal women with HR+/HER2- stage II-III breast cancer received neoadjuvant exemestane at conventional dose of 25mg plus sunitinib in a 3 + 3 design at 25mg (3/1weeks scheme) or 37.5mg continuous dose, for 6 months. Coprimary endpoints were the recommended dose of sunitinib combined with exemestane and objective response. Secondary endpoints included safety and biomarkers of early response. For 15 months, 18 patients were enrolled, 15 at sunitinib 25mg and 3 at 37.5mg. Median age was 73, 77% of patients had T2 tumors and 67% node-positive disease. The most common grade 2 toxicity was asthenia (44%), as was hypertension (22%) for grade 3. No grade 4-5 were reported. Twelve patients (66%) achieved an objective response. VEGFR-2 levels significantly decreased after one month of treatment. Differential gene expression analysis showed downregulation of ESR1, PGR and NAT1 in post-treatment samples and upregulation of EGFR, MYC, SFRP1, and FOXC1. PAM50 analysis on 83% of patients showed a prevalence of luminal A subtype, both in pre-treatment (63.6%) and post-treatment tumors (54.5%). Sunitinib plus exemestane was associated with substantial yet reversible toxicities, providing safety, efficacy and biological impact insights of combining an antiangiogenic drug with hormone therapy in early-stage breast cancer.Trial registration: Registered with ClinicalTrials.gov, NCT00931450. 02/07/2009.
Identifiants
pubmed: 39384801
doi: 10.1038/s41598-024-72152-1
pii: 10.1038/s41598-024-72152-1
doi:
Substances chimiques
exemestane
NY22HMQ4BX
Sunitinib
V99T50803M
Androstadienes
0
Receptor, ErbB-2
EC 2.7.10.1
Receptors, Estrogen
0
Receptors, Progesterone
0
ERBB2 protein, human
EC 2.7.10.1
Biomarkers, Tumor
0
Banques de données
ClinicalTrials.gov
['NCT00931450']
Types de publication
Journal Article
Clinical Trial, Phase II
Clinical Trial, Phase I
Langues
eng
Sous-ensembles de citation
IM
Pagination
23626Informations de copyright
© 2024. The Author(s).
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