Combined Immunotherapies in Metastatic ER+ Breast Cancer
Combined Immunotherapies in Metastatic ER+ Breast Cancer
Women with Hormone Receptor (HR)+ Human Epidermal growth factor Receptor (HER)2- metastatic
 breast cancer are eligible to a randomized trial. Patients receiving standard first line
 therapy for metastatic HR+ Breast cancer(BC) (letrozole+palbociclib) are randomly assigned to
 also receive Stereotactic Body Radiation Therapy(SBRT) to each metastatic lesion.
Inclusion Criteria:

 -  Female ≥ 18 years of age pre and post-menopausal

 -  Metastatic disease (≤ 5 sites of measurable disease)

 -  Eligible for treatment with CDK4/6 + aromatase inhibitors

 -  Premenopausal status is defined as either:

 -  Patient had last menstrual period within the last 12 months, OR

 -  If on tamoxifen or toremifene within the past 14 days, plasma estradiol and FSH must
 be in the premenopausal range per local normal range, OR

 -  In case of therapy-induced amenorrhea, plasma estradiol and/or FSH must be in the
 premenopausal range per local normal range.

 -  Patients who have undergone bilateral oophorectomy are eligible.

 -  Post-menopausal status defined as either 1) at least 2 years without menstrual period
 or 2) patients older than 50 with serological evidence of post-menopausal status or 3)
 hysterectomized patients of any age with FSH confirmation of post-menopausal status.

 -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

 -  Biopsy proven diagnosis of HR+HER2- metastatic breast cancer. ER expression is >10%

 -  Patient needs to be able to understand and demonstrate a willingness to sign a written
 informed consent document

 -  Hematological WBC ≥ 2000/uL

 -  Absolute neutrophil count (ANC) ≥1500/µL

 -  Platelets ≥100 000/µL

 -  Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La Renal Creatinine OR Measured or calculated
 creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN
 OR

 ≥30 mL/min for the participant with creatinine levels >1.5 × institutional ULN Hepatic
 Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total
 bilirubin levels >1.5 × ULN

 -  AST (SGOT) and ALT (SGPT) ≤2.5 × ULN

 -  Coagulation International normalized ratio (INR) OR prothrombin time (PT)

 -  Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless the participant is
 receiving anticoagulant therapy if PT or aPTT is within the therapeutic range of
 intended use of anticoagulants

 Exclusion Criteria:

 -  Active connective tissue disorders, such as lupus or scleroderma requiring flare
 therapy

 -  Current use of systemic chemotherapy, endocrine therapy or HER2-neu targeted therapy

 -  Male breast cancer patients

 -  Any lesion >5 cm in greatest diameter.

 -  Inability to obtain histologic proof of metastatic breast cancer

 -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
 (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
 immunosuppressive therapy within 7 days prior to the first dose of study drug.

 -  Has a known additional malignancy (second primary) that is progressing or has required
 active treatment within the past 3 years. Note: Participants with basal cell carcinoma
 of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. cervical
 cancer in situ) that have undergone potentially curative therapy are not excluded.

 -  Has active autoimmune disease that has required systemic treatment in the past 2 years
 (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
 drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
 replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
 form of systemic treatment.

 -  Has an active infection requiring systemic therapy. Has a known history of Human
 Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by
 local health authority.

 -  Has known psychiatric or substance abuse disorders that would interfere with
 cooperation with the requirements of the trial.

 -  Patients with uncontrolled brain metastases