https://scholars.lib.ntu.edu.tw/handle/123456789/477687
Title: | Potent cell-cycle inhibition and upregulation of immune response with abemaciclib and anastrozole in Neomonarch, phase II neoadjuvant study in HR+/HER2- Breast cancer | Authors: | Hurvitz S.A. Martin M. Press M.F. Chan D. Fernandez-Abad M. Petru E. Rostorfer R. Guarneri V. CHIUN-SHENG HUANG Barriga S. Wijayawardana S. Brahmachary M. Ebert P.J. Hossain A. Liu J. Abel A. Aggarwal A. Jansen V.M. Slamon D.J. |
Issue Date: | 2020 | Publisher: | American Association for Cancer Research Inc. | Journal Volume: | 26 | Journal Issue: | 3 | Start page/Pages: | 566-580 | Source: | Clinical Cancer Research | Abstract: | Purpose: neoMONARCH assessed the biological effects of abemaciclib in combination with anastrozole in the neoadjuvant setting. Patients and Methods: Postmenopausal women with stage I–IIIB HR+/HER2- breast cancer were randomized to a 2-week lead-in of abemaciclib, anastrozole, or abemaciclib plus anastrozole followed by 14 weeks of the combination. The primary objective evaluated change in Ki67 from baseline to 2 weeks of treatment. Additional objectives included clinical, radiologic, and pathologic responses, safety, as well as gene expression changes related to cell proliferation and immune response. Results: Abemaciclib, alone or in combination with anastrozole, achieved a significant decrease in Ki67 expression and led to potent cell-cycle arrest after 2 weeks of treatment compared with anastrozole alone. More patients in the abemaciclib-containing arms versus anastrozole alone achieved complete cell-cycle arrest (58%/68% vs. 14%, P < 0.001). At the end of treatment, following 2 weeks lead-in and 14 weeks of combination therapy, 46% of intent-to-treat patients achieved a radiologic response, with pathologic complete response observed in 4%. The most common all-grade adverse events were diarrhea (62%), constipation (44%), and nausea (42%). Abemaciclib, anastrozole, and the combination inhibited cell-cycle processes and estrogen signaling; however, combination therapy resulted in increased cytokine signaling and adaptive immune response indicative of enhanced antigen presentation and activated T-cell phenotypes. Conclusions: Abemaciclib plus anastrozole demonstrated biological and clinical activity with generally manageable toxicities in patients with HR+/HER2- early breast cancer. Abemaciclib led to potent cell-cycle arrest, and in combination with anastrozole, enhanced immune activation. ? 2020 American Association for Cancer Research. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85077154862&doi=10.1158%2f1078-0432.CCR-19-1425&partnerID=40&md5=2fd5f64b97103cb9d8f41f77458ab88a https://scholars.lib.ntu.edu.tw/handle/123456789/477687 |
ISSN: | 1078-0432 | DOI: | 10.1158/1078-0432.CCR-19-1425 | SDG/Keyword: | abemaciclib; alanine aminotransferase; anastrozole; aspartate aminotransferase; cytokine; estrogen; estrogen receptor; Ki 67 antigen; progesterone receptor; abemaciclib; aminopyridine derivative; anastrozole; antineoplastic agent; benzimidazole derivative; CDK4 protein, human; CDK6 protein, human; cyclin dependent kinase 4; cyclin dependent kinase 6; epidermal growth factor receptor 2; ERBB2 protein, human; ESR1 protein, human; estrogen receptor alpha; progesterone receptor; abdominal pain; adaptive immunity; adult; aged; alanine aminotransferase blood level; antigen presentation; Article; aspartate aminotransferase blood level; breast cancer; cancer combination chemotherapy; cancer staging; cell cycle arrest; cell proliferation; constipation; controlled study; decreased appetite; diarrhea; drug response; drug safety; dysgeusia; fatigue; female; gene; gene expression; gene mutation; headache; histopathology; hot flush; human; immune response; intention to treat analysis; leukopenia; major clinical study; middle aged; monotherapy; multicenter study; multiple cycle treatment; nausea; neoadjuvant chemotherapy; neutropenia; open study; pathologic complete response; phase 2 clinical trial; PIK3CA gene; postmenopause; priority journal; radiodiagnosis; randomized controlled trial; rash; side effect; signal transduction; T lymphocyte activation; treatment duration; upregulation; very elderly; breast tumor; cell cycle checkpoint; clinical trial; drug effect; immunology; metabolism; neoadjuvant therapy; pathology; patient safety; physiology; procedures; treatment outcome; Adaptive Immunity; Adult; Aged; Aged, 80 and over; Aminopyridines; Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Breast Neoplasms; Cell Cycle Checkpoints; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Estrogen Receptor alpha; Female; Humans; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Patient Safety; Postmenopause; Receptor, ErbB-2; Receptors, Progesterone; Treatment Outcome [SDGs]SDG3 |
Appears in Collections: | 醫學系 |
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