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

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

Research output: Contribution to journalArticle

1 Scopus citations

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. 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.

Original languageEnglish (US)
Pages (from-to)188-196
Number of pages9
JournalClinical breast cancer
Volume19
Issue number3
DOIs
StatePublished - Jun 2019

Keywords

  • Endocrine-resistant

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Paplomata, E., Zelnak, A., Santa-Maria, C. A., Liu, Y., Gogineni, K., Li, X., Moreno, C. S., Chen, Z., Kaklamani, V., & O'Regan, R. M. (2019). Use of Everolimus and Trastuzumab in Addition to Endocrine Therapy in Hormone-Refractory Metastatic Breast Cancer. Clinical breast cancer, 19(3), 188-196. https://doi.org/10.1016/j.clbc.2018.12.017