BM can be an important cause of morbidity and mortality in breast cancer. In addition to mechanisms of endocrine therapy resistance, like ESR1 mutations, BM have other causes of resistance such as inherent resistance to systemic therapy and limited drug tissue penetration. We have shown imlunestrant has activity in ER-dependent cell lines and
ER+ breast cancer cell lines and mouse models with ESR1 wild-type or mutant tumors were treated with imlunestrant alone or with abemaciclib, alpelisib or everolimus. Effects on ER degradation, ER-mediated gene expression, cell proliferation and viability were examined
Across cell lines, imlunestrant degraded ER and decreased ER-mediated gene expression. In addition, cell proliferation and tumor growth in ESR1-wild type and mutant models was significantly inhibited by imlunestrant. Combination of imlunestrant with abemaciclib, alpelisib or everolimus further enhanced the efficacy across cell lines and
Imlunestrant, a novel potent and orally available SERD, demonstrated activity across a panel of breast cancer cell lines and decreased tumor burden in both ESR1-wild type and mutant xenograft and PDX models. Imlunestrant also demonstrated CNS penetrance and improved survival in a brain orthotopic model. Imlunestrant is being evaluated in multiple global phase III clinical trials in metastatic and early breast cancer.
Drs. Cecilia Mur and Matthew VandeKopple have equally contributed to the study.
Eli Lilly and Company.
Eli Lilly and Company.
M. VandeKopple, A. Capen, L. Huber, N. Pulliam, M. Dowless, X. Gong: Financial Interests, Personal, Full or part-time Employment: Loxo Oncology at Lilly; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. C. Mur, W. Shen, C. Marugan, M.A. Castanares, D. Garcia-Tapia, B. Mattioni, J. Bastian, J. Manro, M.J. Ortiz Ruiz, M.J. Lallena, A. De Dios: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company.