Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Exploratory biomarkers in MONARCH 1, a phase II study of abemaciclib monotherapy in hormone-receptor positive (HR ) HER2- metastatic breast cancer (MBC)

Date

09 Oct 2016

Session

Basic science and translational research

Presenters

Sara Tolaney

Citation

Annals of Oncology (2016) 27 (6): 1-36. 10.1093/annonc/mdw435

Authors

S.M. Tolaney1, J. Cortes Castan2, M.N. Dickler3, E. Zamora2, C.W. Caldwell4, T.S. Nguyen5, S. Nanda5, A. Koustenis6, H.S. Rugo7

Author affiliations

  • 1 Breast Oncology Center, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 2 Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Barcelona/ES
  • 3 Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York/US
  • 4 Diagnostic And Experimental Pathology, Eli Lilly and Company, Indianapolis/US
  • 5 Statistics/oncology, Eli Lilly and Company, Indianapolis/US
  • 6 Oncology, Eli Lilly and Company, 46285 - Indianapolis/US
  • 7 Medicine (hematology/oncology), University of California San Francisco Comprehensive Cancer Center, San Francisco/US
More

Resources

Abstract 2380

Background

Abemaciclib is a selective inhibitor of CDK4 & 6 that is dosed orally on a continuous schedule. In the MONARCH 1 phase II study (NCT02102490), abemaciclib monotherapy demonstrated antitumor activity with an objective response rate of 19.7% and a clinical benefit rate (CBR = PR + SD ≥ 6 months) of 42.4% in women with previously treated HR+ HER2- MBC whose disease had progressed on or after prior endocrine therapy and who had received 1-2 prior chemotherapies in the metastatic setting.

Methods

Exploratory biomarker analyses of paired pre- and on-treatment blood exosomes and formalin-fixed paraffin-embedded (FFPE) archival tumor tissues from patients in MONARCH 1 were performed. Exosomal preparations from baseline samples (n = 68), day 15 of cycle 1 (C1D15) treatment (n = 68), and samples following treatment discontinuation (n = 59) were analyzed as a novel “liquid biopsy” using an automated multi-modal multiplexed platform (Modaplex, QIAGEN). FFPE tumors (n = 77) were also analyzed for mRNA expression of cell cycle related genes as well as normal reduction mammoplasty tissues (n = 19) for comparison.

Results

In blood, analysis at C1D15 revealed several changes in mRNA levels of cell-cycle related genes, including decreases in E2F1-4, and an increase in CCND1; these changes reverted following treatment discontinuation. For baseline exosome samples, notable differences were observed in some mRNAs compared to archival tumor. Cell cycle mRNA expression profiles were distinct in FFPE tumors of MBC patients compared to normal breast tissues. In single marker analysis of tumors, higher mRNA levels of retinoblastoma (RB) correlated with specific efficacy outcomes including disease control rate (DCR = PR + SD), CBR, PFS, and treatment duration (p < 0.05); some associations were also observed for other genes. In multi-marker analysis, mRNA levels of RB1, CCND1, CCNE1, cMYC, and CDK2 further identified response sub-groups.

Conclusions

Changes in mRNAs by C1D15 included inhibition of proliferation genes; cessation of treatment resulted in a reversal. Higher tissue levels of RB mRNAs correlated with DCR, CBR, PFS, and treatment duration.

Clinical trial identification

NCT02102490

Legal entity responsible for the study

Eli Lilly and Company

Funding

Eli Lilly and Company

Disclosure

S.M. Tolaney: Research funding from Genentech, Exelixis, Pfizer, and Novartis. J. Cortes: Honoraria from Roche, Celgene, Novartis, and Eisai. Consulting/advisory role for Roche, Celgene. M.N. Dickler: Advisor/board member of Eli Lilly and Company. Received grants/research support from Eli Lilly and Company. C.W. Caldwell: Employee and stockholder of Eli Lilly and Company Experimental. T.S. Nguyen, S. Nanda, A. Koustenis: Employee and stockholder of Eli Lilly and Company. H.S. Rugo: Plexxikon, Macrogenics, OBI Pharma, Eisai, Pfizer, Novartis, Eli Lilly, GlaxoSmithKline, Genentech, Celsion, Nektar, Merck. Travel expenses: Novartis, Nektar, Roche/Genentech, OBI Pharma, Mylan. Honoraria, speaker's bureau: Genomic Health. All other authors have declared no conflicts of interest.

Resources from the same session

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings