Use of Everolimus and Trastuzumab in Addition to Endocrine Therapy in Hormone-Refractory Metastatic Breast Cancer

Elisavet Paplomata, Amelia Zelnak, Cesar Santa-Maria, Yuan Liu, Keerthi Gogineni, Xiaoxian Li, Carlos S. Moreno, Zhengjia Chen, Virginia Kaklamani, Ruth M. O'Regan

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalClinical Breast Cancer
DOIs
StatePublished - Jan 1 2019

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Hormones
Breast Neoplasms
Therapeutics
Disease-Free Survival
Disease Progression
Everolimus
Trastuzumab
Growth Factor Receptors
Sirolimus
Safety
Drug Therapy
Neoplasms

Keywords

  • Endocrine-resistant

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Use of Everolimus and Trastuzumab in Addition to Endocrine Therapy in Hormone-Refractory Metastatic Breast Cancer. / Paplomata, Elisavet; Zelnak, Amelia; Santa-Maria, Cesar; Liu, Yuan; Gogineni, Keerthi; Li, Xiaoxian; Moreno, Carlos S.; Chen, Zhengjia; Kaklamani, Virginia; O'Regan, Ruth M.

In: Clinical Breast Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Paplomata, Elisavet ; Zelnak, Amelia ; Santa-Maria, Cesar ; Liu, Yuan ; Gogineni, Keerthi ; Li, Xiaoxian ; Moreno, Carlos S. ; Chen, Zhengjia ; Kaklamani, Virginia ; O'Regan, Ruth M. / Use of Everolimus and Trastuzumab in Addition to Endocrine Therapy in Hormone-Refractory Metastatic Breast Cancer. In: Clinical Breast Cancer. 2019.
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abstract = "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.",
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AU - Zelnak, Amelia

AU - Santa-Maria, Cesar

AU - Liu, Yuan

AU - Gogineni, Keerthi

AU - Li, Xiaoxian

AU - Moreno, Carlos S.

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AU - O'Regan, Ruth M.

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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.

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