TY - JOUR
T1 - Abemaciclib in Combination With Endocrine Therapy for Patients With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer
T2 - A Phase 1b Study
AU - Tolaney, Sara M.
AU - Beeram, Muralidhar
AU - Beck, J. Thaddeus
AU - Conlin, Alison
AU - Dees, E. Claire
AU - Puhalla, Shannon L.
AU - Rexer, Brent N.
AU - Burris, Howard A.
AU - Jhaveri, Komal
AU - Helsten, Teresa
AU - Becerra, Carlos
AU - Kalinsky, Kevin
AU - Moore, Kathleen N.
AU - Manuel, Allison M.
AU - Lithio, Andrew
AU - Price, Gregory L.
AU - Chapman, Sonya C.
AU - Litchfield, Lacey M.
AU - Goetz, Matthew P.
N1 - Publisher Copyright:
Copyright © 2022 Tolaney, Beeram, Beck, Conlin, Dees, Puhalla, Rexer, Burris, Jhaveri, Helsten, Becerra, Kalinsky, Moore, Manuel, Lithio, Price, Chapman, Litchfield and Goetz.
PY - 2022/2/10
Y1 - 2022/2/10
N2 - 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.
AB - 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.
KW - CDK4
KW - CDK6
KW - abemaciclib
KW - endocrine therapy
KW - metastatic breast cancer
UR - http://www.scopus.com/inward/record.url?scp=85125299662&partnerID=8YFLogxK
U2 - 10.3389/fonc.2021.810023
DO - 10.3389/fonc.2021.810023
M3 - Article
C2 - 35223458
AN - SCOPUS:85125299662
SN - 2234-943X
VL - 11
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 810023
ER -