Phase 2
N=237
A Study of Abemaciclib (LY2835219) in Women With HR+, HER2+ Locally Advanced or Metastatic Breast Cancer
Hormone Receptor Positive Breast Cancer · HER-2 Positive Breast Cancer
Bottom Line
View on ClinicalTrials.gov: NCT02675231 ↗Enrolled (actual)
237
Serious AEs
23.4%
Results posted
May 2020
Primary outcome: Primary: Progression Free Survival (PFS) — 8.3; 5.7; 5.7 Months — p=0.0506
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Abemaciclib (Drug); Trastuzumab (Drug); Fulvestrant (Drug); Standard of Care Single Agent Chemotherapy (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Female
- Sponsor
- Eli Lilly and Company
- Primary completion
- Apr 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression Free Survival (PFS) |
8.3; 5.7; 5.7 | 0.0506 |
| SECONDARY Percentage of Participants With 1 Year Overall Survival (OS) |
77.2; 77.4; 69.8 | 0.241 |
| SECONDARY Percentage of Participants With 2 Year OS |
55.8; 55.7; 43.0 | 0.104 |
| SECONDARY Percentage of Participants With 3 Year OS |
46.7; 40.2; 29.9 | 0.049 sig |
| SECONDARY Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR) |
32.9; 13.9; 13.9 | — |
| SECONDARY Duration of Response (DoR) |
12.5; 9.5; NA | — |
| SECONDARY Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR) |
78.5; 74.7; 67.1 | — |
| SECONDARY Percentage of Participants With Best Overall Response of CR, PR, or SD With Duration of SD for at Least 6 Months: Clinical Benefit Rate (CBR) |
58.2; 45.6; 38.0 | — |
| SECONDARY Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) |
0; 0.20; 0.31 | 0.232 |
| SECONDARY Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) |
-2.9; -5.9; -1.9; -1.0; -4.4; -4.5 | 0.689 |
| SECONDARY Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score |
0.01; -0.01; -0.04 | 0.033 sig |
| SECONDARY Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) |
0.61; -1.64; -0.61 | 0.546 |
| SECONDARY Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib and Its Metabolites (M2 and M20) |
134; 155; 72.0; 96.5; 136; 181 | — |
Summary
The purpose of this study is to evaluate the effectiveness of abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus physicians choice standard of care chemotherapy in women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 positive (HER2+) locally advanced or metastatic breast cancer after prior exposure to at least two HER2-directed therapies for advanced disease.
Eligibility Criteria
Inclusion Criteria
- diagnosis of HR+, HER2+ breast cancer (BC)
- unresectable locally advanced recurrent BC or metastatic BC
- adequate tumor tissue available prior to randomization
- measurable and/or non-measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- previously received:
- at least 2 HER2-directed therapies for advanced disease
- participant must have received trastuzumab emtansine (T-DM1) in any disease setting
- must have received a taxane in any disease setting
- may have received any endocrine therapy (excluding fulvestrant)
- have postmenopausal status due to surgical / natural menopause or chemical ovarian suppression
- performance status (PS) of 0 to 1 on the Eastern Cooperative Oncology Group scale
- left ventricular ejection fraction (LVEF) of 50% or higher at baseline
- adequate organ function
- negative serum pregnancy test at baseline (within 14 days prior to randomization) and agree to use medically approved precautions to prevent pregnancy during the study and for 12 weeks following the last dose of abemaciclib if menopause induced by gonadotropin-releasing hormone (GnRH) agonist or radiation
- discontinued previous localized radiotherapy for palliative purposes or for lytic lesions at risk of fracture at least 2 weeks prior to randomization and recovered from the acute effects of therapy
- discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, and endocrine therapy), except trastuzumab, for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy
- are able to swallow capsules
Exclusion Criteria
- have visceral crisis
- known central nervous system (CNS) metastases that are untreated, symptomatic, or require steroids to control symptoms
- had major surgery within 14 days prior to randomization
- received prior treatment with any cyclin-dependent kinase (CDK) 4 and CDK 6 inhibitor
- received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of randomization for a nonmyelosuppressive or myelosuppressive agent, respectively
- have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study
- history within the last 6 months of symptomatic congestive heart failure, myocardial infarction, or unstable angina
- history within the last 12 months of any of the following conditions: syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest
- history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years
- active bacterial, fungal infection, or detectable viral infection
- have received any recent (within 28 days prior to randomization) live virus vaccination
- hypersensitivity to trastuzumab, murine proteins, fulvestrant, or to any of the excipients
Data sourced from ClinicalTrials.gov (NCT02675231). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.