Use of Everolimus and Trastuzumab in Addition to Endocrine Therapy in Hormone-Refractory Metastatic Breast Cancer.
Adult
Aged
Antineoplastic Agents, Hormonal
/ pharmacology
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Breast Neoplasms
/ drug therapy
Drug Resistance, Neoplasm
/ drug effects
Everolimus
/ administration & dosage
Female
Follow-Up Studies
Humans
Middle Aged
Neoplasm Metastasis
Neoplasms, Hormone-Dependent
/ drug therapy
Prognosis
Receptor, ErbB-2
/ metabolism
Receptors, Estrogen
/ metabolism
Receptors, Progesterone
/ metabolism
Survival Rate
Trastuzumab
/ administration & dosage
Endocrine-resistant
Journal
Clinical breast cancer
ISSN: 1938-0666
Titre abrégé: Clin Breast Cancer
Pays: United States
ID NLM: 100898731
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
09
09
2018
revised:
17
12
2018
accepted:
26
12
2018
pubmed:
13
2
2019
medline:
20
6
2020
entrez:
13
2
2019
Statut:
ppublish
Résumé
Increased signaling through growth factor receptor pathways, including HER2, plays a role in resistance to endocrine therapy (ET) in patients with hormone receptor (HR)-positive metastatic breast cancer (MBC). Inhibition of mechanistic target of rapamycin improves outcomes when used in addition to ET in patients with HR-positive MBC, who previously received ET. We hypothesized that the additional use of trastuzumab (T) or everolimus (E) could restore sensitivity to ET in patients with endocrine-resistant, HR-positive, HER2-negative MBC. Patients with endocrine-resistant HR-positive, HER2-negative MBC continued the ET during which they had experienced disease progression, and were randomized to receive T or E. At disease progression, patients could continue the therapy they were receiving and have E or T used in addition. Fifty-four patients were randomized to the additional use of E (n = 30) or T (n = 24) with existing ET. Progression-free survival (PFS) was 5.7 months, and 2.2 months, respectively, and clinical benefit rate at 24 weeks was 48% and 11% for patients receiving E or T, respectively. PFS was 4.5 months and 3.1 months for patients in whom E (n = 16) or T (n = 12) was used post progression, respectively. There were no new safety signals apart from 2 patients who had a decreased ejection fraction while receiving E with ET. These results suggest that E, but not T, can potentially reverse resistance to ET in patients with endocrine-resistant HR-positive, HER2-negative MBC. Further, the additional use of E with an ET to which the cancer has already been exposed might offer the possibility of delaying time to use of chemotherapy.
Sections du résumé
BACKGROUND
Increased signaling through growth factor receptor pathways, including HER2, plays a role in resistance to endocrine therapy (ET) in patients with hormone receptor (HR)-positive metastatic breast cancer (MBC). Inhibition of mechanistic target of rapamycin improves outcomes when used in addition to ET in patients with HR-positive MBC, who previously received ET. We hypothesized that the additional use of trastuzumab (T) or everolimus (E) could restore sensitivity to ET in patients with endocrine-resistant, HR-positive, HER2-negative MBC.
PATIENTS AND METHODS
Patients with endocrine-resistant HR-positive, HER2-negative MBC continued the ET during which they had experienced disease progression, and were randomized to receive T or E. At disease progression, patients could continue the therapy they were receiving and have E or T used in addition.
RESULTS
Fifty-four patients were randomized to the additional use of E (n = 30) or T (n = 24) with existing ET. Progression-free survival (PFS) was 5.7 months, and 2.2 months, respectively, and clinical benefit rate at 24 weeks was 48% and 11% for patients receiving E or T, respectively. PFS was 4.5 months and 3.1 months for patients in whom E (n = 16) or T (n = 12) was used post progression, respectively. There were no new safety signals apart from 2 patients who had a decreased ejection fraction while receiving E with ET.
CONCLUSION
These results suggest that E, but not T, can potentially reverse resistance to ET in patients with endocrine-resistant HR-positive, HER2-negative MBC. Further, the additional use of E with an ET to which the cancer has already been exposed might offer the possibility of delaying time to use of chemotherapy.
Identifiants
pubmed: 30745109
pii: S1526-8209(18)30637-2
doi: 10.1016/j.clbc.2018.12.017
pii:
doi:
Substances chimiques
Antineoplastic Agents, Hormonal
0
Receptors, Estrogen
0
Receptors, Progesterone
0
Everolimus
9HW64Q8G6G
ERBB2 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Trastuzumab
P188ANX8CK
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
188-196Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR002378
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.