TY - JOUR
T1 - Use of Everolimus and Trastuzumab in Addition to Endocrine Therapy in Hormone-Refractory Metastatic Breast Cancer
AU - Paplomata, Elisavet
AU - Zelnak, Amelia
AU - Santa-Maria, Cesar A.
AU - Liu, Yuan
AU - Gogineni, Keerthi
AU - Li, Xiaoxian
AU - Moreno, Carlos S.
AU - Chen, Zhengjia
AU - Kaklamani, Virginia
AU - O'Regan, Ruth M.
N1 - Funding Information:
A.Z. has served as an advisor/consultant for Astra Zeneca and Pfizer; C.A.S.-M. has research funding from Pfizer and MedImmune; V.K. has served as an advisor/consultant and is on speakers bureaus for Astra Zeneca, Pfizer, and Genentech; R.M.O. has served as an advisor/consultant for Novartis, Genentech, Pfizer, Eli-Lilly, PUMA, Macrogenics, Immunomedics, Genomic Health, and Biotheranostics and has grant funding from Novartis, Eisai, and Pfizer; E.P. has received research funding from Novartis, Genentech, Corcept Therapeutics, Seattle Genetics, Abbvie, Merck, and Hoosier Research Cancer Network. The remaining authors have stated that they have no conflicts of interest.This trial was sponsored by Genentech, who additionally supplied trastuzumab, and everolimus was supplied by Novartis. We would like to thank the Glenn Family Breast Cancer Foundation for their support of the Emory Breast Program. The correlative studies reported in this publication were supported in part by Developmental Funds from the Crouse Fund for Breast Cancer Research, as well as by the Emory Integrated Genomics Core (EIGC) Shared Resource and NIH/NCI under award number UL1TR002378. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
A.Z. has served as an advisor/consultant for Astra Zeneca and Pfizer; C.A.S.-M. has research funding from Pfizer and MedImmune ; V.K. has served as an advisor/consultant and is on speakers bureaus for Astra Zeneca, Pfizer, and Genentech; R.M.O. has served as an advisor/consultant for Novartis, Genentech, Pfizer, Eli-Lilly, PUMA, Macrogenics, Immunomedics, Genomic Health, and Biotheranostics and has grant funding from Novartis , Eisai , and Pfizer ; E.P. has received research funding from Novartis , Genentech , Corcept Therapeutics , Seattle Genetics , Abbvie , Merck , and Hoosier Research Cancer Network . The remaining authors have stated that they have no conflicts of interest.
Funding Information:
This trial was sponsored by Genentech , who additionally supplied trastuzumab, and everolimus was supplied by Novartis . We would like to thank the Glenn Family Breast Cancer Foundation for their support of the Emory Breast Program. The correlative studies reported in this publication were supported in part by Developmental Funds from the Crouse Fund for Breast Cancer Research, as well as by the Emory Integrated Genomics Core (EIGC) Shared Resource and NIH / NCI under award number UL1TR002378. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2019 The Authors
PY - 2019/6
Y1 - 2019/6
N2 - 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. Patients with endocrine-refractory, hormone receptor-positive, HER2-negative metastatic breast cancer were treated with everolimus (n = 30) or trastuzumab (n = 24) in addition to their existing endocrine therapy. We hypothesized that the combination could restore sensitivity to endocrine therapy. Progression-free survival was 5.7 months, and 2.2 months, and clinical benefit rate at 24 weeks was 48% and 11% for patients who received everolimus or trastuzumab, respectively.
AB - 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. Patients with endocrine-refractory, hormone receptor-positive, HER2-negative metastatic breast cancer were treated with everolimus (n = 30) or trastuzumab (n = 24) in addition to their existing endocrine therapy. We hypothesized that the combination could restore sensitivity to endocrine therapy. Progression-free survival was 5.7 months, and 2.2 months, and clinical benefit rate at 24 weeks was 48% and 11% for patients who received everolimus or trastuzumab, respectively.
KW - Endocrine-resistant
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U2 - 10.1016/j.clbc.2018.12.017
DO - 10.1016/j.clbc.2018.12.017
M3 - Article
C2 - 30745109
AN - SCOPUS:85061105613
VL - 19
SP - 188
EP - 196
JO - Clinical Breast Cancer
JF - Clinical Breast Cancer
SN - 1526-8209
IS - 3
ER -