Anastrozole, Fulvestrant, and Abemaciclib for the Treatment of Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer

Inclusion Criteria

• Patients must have a current diagnosis of hormone receptor positive (HR+) and HER2 negative (-) breast cancer. * To fulfill the requirement of HR+ disease, a breast cancer must express, by immunohistochemistry (IHC), at least one of the hormone receptors (estrogen receptor [ER] or, progesterone receptor [PgR]) as defined in the relevant American Society of Clinical Oncology (ASCO) (Velasco-Velazquez, Li et al.)/College of American Pathologists (CAP) (Abbott, Abbott et al.) Guidelines (Hammond et al. 2010). For ER and PgR assays to be considered positive, >= 1% of tumor cell nuclei must be immunoreactive by IHC (Hammond et al. 2010). * To fulfill the requirement of HER2- disease, a breast cancer must not express overexpression of HER2 by either IHC or in-situ hybridization (Rumi, Sato et al.) as defined in the relevant ASCO/CAP guidelines (Wolff et al. 2013)
• Patients must have newly diagnosed metastatic regional breast cancer (stage IV per American Joint Committee on Cancer [AJCC] 8th edition criteria for staging of breast cancer) or local-regional advanced or recurrent cancer not amenable to curative treatment * Relapse > 12 months from completion of neoadjuvant and/or adjuvant endocrine and/or chemotherapy with no treatment for advanced or metastatic disease is allowed. * Patients with visceral metastasis, including brain metastasis, are included.
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Have at least one measurable disease as defined per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
• Hemoglobin > 8 g/dL * Patients may receive transfusion of packed red blood cells (PRBC) to achieve this hemoglobin level at the discretion of the investigator; however, initial study drug treatment must not begin earlier than the day after the PRBC transfusion
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcl
• Total bilirubin =< 1.5 X institutional upper limit of normal (ULN) * Patients with Gilbert’s syndrome with a total bilirubin =< 2.0 times ULN and direct bilirubin within normal limits are permitted
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional ULN
• Creatinine =< 1.5 X institutional ULN
• Able to swallow oral medications
• Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade =< 1) from the acute effects of chemotherapy except for residual alopecia (of any grade) or Grade 2 peripheral neuropathy prior to enrollment. A washout period of at least 12 months is required between last chemotherapy dose and enrollment (provided the patient did not receive radiotherapy)
• Women of child-bearing potential (WOCBP) (i.e. premenopausal) and men must agree to initiate ovarian or testicular suppression, for the duration of treatment participation, and for 90 days following completion of therapy. * A post-menopausal female patient is defined by one of the following for female patients: prior bilateral oophorectomy, age ≥ 60 years, age < 60 and amenorrheic (non-treatment-induced amenorrhea secondary to tamoxifen, toremifene, ovarian suppression, or chemotherapy) for at least 12 months. * If follicle-stimulating hormone (FSH) and estradiol labs were performed as standard practice within the screening window and the patient is post-menopausal, those lab results must be in the postmenopausal range. These labs are not required to be performed for the study
• WOCBP are required to initiate effective contraception by study intervention start. Effective contraception is per the investigator’s discretion. A WOCBP (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) is someone who meets at least one of the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Must be able to sign a written informed consent, are reliable, willing to be available for the duration of the study and are willing to follow study procedures
• Both men and women and members of all races and ethnic groups are eligible for this trial. Non-English speaking, deaf, hard of hearing and illiterate individuals are eligible for this trial.

Exclusion Criteria

• Localized breast cancer, which is curable with surgery or radiation, with or without chemotherapy. This study will utilize the American Joint Committee on Cancer (AJCC) staging system, eighth edition that provides a strategy for grouping patients with respect to prognosis. The AJCC has designated staging by tumor, node, metastasis (TNM) classification. The researchers will also review tumor size, lymph node status, and estrogen-receptor and progesterone-receptor levels in the tumor tissue
• Current diagnosis of inflammatory breast cancer.
• Patients who have had chemotherapy or radiotherapy within 12 months prior to entering the study. * (Note: For the current diagnosis, CDK 4/6 inhibitor and/or endocrine therapy initiated within 8 weeks prior to starting study intervention is allowed)
• Prior treatment with fulvestrant
• Patients are currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study. If a patient is currently enrolled in a clinical trial involving non-approved use of a device, then agreement with the principal investigator is required to establish eligibility
• Have serious pre-existing medical conditions that, in the judgment of the investigator, would preclude participation in this study (e.g., history of major surgical resection involving the stomach or small bowel, preexisting Crohn’s disease or ulcerative colitis, interstitial lung disease, severe dyspnea at rest, psychiatric illness/social situations that would limit compliance with study requirements, or any pre-existing chronic condition resulting in baseline grade 2 or higher diarrhea.
• Have a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation or sudden cardiac arrest
• Have a history of any other cancer (except for non-melanoma skin cancer or carcinoma in situ of the cervix) unless in complete remission with no therapy for a minimum of three years or have received an autologous or allogeneic stem-cell transplant (>= 5 years from stem cell transplant is acceptable). (Patients with non-active cancer not requiring treatment are allowed to be enrolled on the study)
• Have an active bacterial or fungal infection or a detectable viral infection (e.g., human immunodeficiency virus [HIV] or viral hepatitis). Lab tests for these conditions are not required for enrollment unless there is clinical suspicion following standard of care procedures.
• Recent therapy with a monoclonal therapy is excluded. Wash out of at least three half-lives of a monoclonal antibody would be required to be enrolled
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to CDK4/6 inhibitors or other agents used in study
• Patients who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants