Abemaciclib in Combination With Endocrine Therapy for Patients With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: A Phase 1b Study

• Type of Material: Article
• Authors: Sara M Tolaney, Dana-Farber Cancer Institute; Muralidhar Beeram, South Texas Accelerated Res Therapeut; Thaddeus J Beck, Highlands Oncology; Alison Conlin, Providence Cancer Center; Claire Dees, University of North Carolina Chapel Hill; Shannon L Puhalla, University of Pittsburgh; Brent N Rexer, Vanderbilt University; Howard A Burris III, Tennessee Oncology; Komal Jhaveri, Memorial Sloan Kettering Cancer Center; Teresa Helsten, University of California San Diego; Carlos Becerra, Texas Oncology; Kevin Kalinsky, Emory University; Kathleen N Moore, University of Oklahoma; Allison M Manuel, Eli Lilly and Company; Andrew Lithio, Eli Lilly and Company; Gregory L Price, Eli Lilly and Company; Sonya C Chapman, Eli Lilly and Company; Lacey M Litchfield, Eli Lilly and Company; Matthew P Goetz, Mayo Clinic
• Language: English
• Date: 2022-02-10
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Tolaney, Beeram, Beck, Conlin, Dees, Puhalla, Rexer, Burris, Jhaveri, Helsten, Becerra, Kalinsky, Moore, Manuel, Lithio, Price, Chapman, Litchfield and Goetz
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fonc.2021.810023
• Title of Journal or Parent Work: FRONTIERS IN ONCOLOGY
• Volume: 11
• Start Page: 810023
• End Page: 810023
• Grant/Funding Information: This study was sponsored by Eli Lilly and Company.
• Keywords: Oncology; endocrine therapy; Life Sciences & Biomedicine; abemaciclib; INHIBITOR; INITIAL THERAPY; metastatic breast cancer; CDK6; CDK4; Science & Technology
• Research Categories: Health Sciences, Oncology; Health Sciences, Pharmacology

Abstract

Background: Cyclin-dependent kinases (CDK) 4 and 6 regulate G1 to S cell cycle progression and are often altered in cancers. Abemaciclib is a selective inhibitor of CDK4 and CDK6 approved for administration on a continuous dosing schedule as monotherapy or as combination therapy with an aromatase inhibitor or fulvestrant in patients with advanced or metastatic breast cancer. This Phase 1b study evaluated the safety and tolerability, pharmacokinetics, and antitumor activity of abemaciclib in combination with endocrine therapy for metastatic breast cancer (MBC), including aromatase inhibitors (letrozole, anastrozole, or exemestane) or tamoxifen. Patients and Methods: Women ≥18 years old with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) MBC were eligible for enrollment. Eligibility included measurable disease or non-measurable but evaluable bone disease by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1, Eastern Cooperative Oncology Group performance status 0–1, and no prior chemotherapy for metastatic disease. Adverse events were graded by the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 and tumor response were assessed by RECIST v1.1. Results: Sixty-seven patients were enrolled and received abemaciclib 200 mg every 12 hours in combination with letrozole (Part A, n=20), anastrozole (Part B, n=16), tamoxifen (Part C, n=16), or exemestane (Part D, n=15). The most common treatment-emergent adverse events (TEAE) were diarrhea, fatigue, nausea, and abdominal pain. Grade 4 TEAEs were reported in five patients (one each with hyperglycemia, hypertension, neutropenia, procedural hemorrhage, and sepsis). There was no effect of abemaciclib or endocrine therapy on the pharmacokinetics of any combination study drug. Across all treated patients, the median progression-free survival was 25.4 months (95% confidence interval: 18.0, 35.8). The objective response rate was 38.9% in 36 patients with measurable disease. Conclusions: Abemaciclib in combination with multiple endocrine therapy options exhibited manageable safety and promising antitumor activity in patients with HR+, HER2- MBC. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT02057133.