This is a single arm study of abemaciclib and endocrine therapy with stereotactic radiosurgery (SRS) among patients with hormone receptor (HR)+/HER2- metastatic breast cancer brain metastases.
HR+ breast cancer to fulfill the requirement of HR+ disease, a breast cancer must express (≥ 1%), by immunohistochemistry (IHC), at least 1 of the hormone receptors (estrogen receptor [ER] or progesterone receptor [PR]) as defined in the American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) Guidelines
To fulfill the requirement of HER2- disease, a breast cancer must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of HER2 by either IHC or in-situ hybridization as defined by the ASCO / CAP Guidelines
≤ 15 brain metastases eligible for stereotactic radiation
Able to swallow oral medications
Presence of leptomeningeal disease
Prior receipt of whole brain radiation therapy
Prior receipt of abemaciclib in the setting of brain metastases or in the past 6 months for the treatment of metastatic disease.
All toxicities attributed to prior anticancer therapy must have been resolved to Grade 1 (NCI CTCAE Version 5) or baseline before administration of study drug(s) other than: a. Toxicities attributed to prior anticancer therapy that either are not expected to resolve and/or result in long-lasting sequelae, such as neuropathy after platinum-based therapy b. Toxicities that are not expected to interfere with study treatment, such as fatigue, alopecia, or grade 2 hematologic toxicity
Sequential
Stereotactic Radiosurgery (SRS)
RadiationPatients will receive single session SRS to intact brain metastases and post-operative cavities. For intact brain metastases, this will be 15 Gy to lesions between 31-40 mm, 18 Gy to 21- 30 mm, and 24 Gy to lesions measuring ≤ 20 mm.
Abemaciclib
DrugAbemaciclib is an orally administered selective small-molecule inhibitor of CDK4 and CDK6 that is 14 times more potent against CDK4 than CDK6 in enzymatic assays that is approved for the treatment of advanced or metastatic breast cancers. Abemaciclib will be administered at a dose of 150 mg twice daily.
Endocrine therapy
DrugAbemaciclib will be administered with standard of care endocrine therapy. Endocrine therapy can consist of fulvestrant or an aromatase inhibitor. Dosing of concurrent endocrine therapy with abemaciclib should follow standard dosing and safety guidelines.
Intracranial Progression Free Survival (PFS)
Intracranial Progression Free Survival: defined as the time from the date of start of treatment to investigator-determined date of progression or death due to any cause, whichever comes first. Progression will be determined by Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) Criteria.
Intracranial local brain tumor control
Intracranial local brain tumor control following SRS and abemaciclib will be determined from irradiated lesions according to RANO-BM criteria.
Intracranial distant brain tumor control
Intracranial distant brain tumor control following SRS and abemaciclib will determined by the development of new lesions outside of the irradiated area.
Extracranial Progression Free Survival
Extracranial Progression Free Survival: Time from the date of start of treatment to the investigator determined date of progression (determined by RECIST) or death due to any cause, whichever occurs first.
Overall Survival
Overall Survival is defined as the time from the start of treatment to death due to any cause.
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H. Lee Moffitt Cancer Center and Research Institute
Lead sponsor
Eli Lilly and Company
Collaborator
