Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Letrozole

Immunomodulating Agents

Palbociclib

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Protein Kinase Inhibitors

Patients randomized to arm 1 will start standard Letrozole followed by Palbociclib at day 21.

Patients randomized to arm 2 will start letrozole alone, and add palbociclib on day 21, after completion of I-SBRT. Treatment may be given daily (to keep the total I-SBRT treatment time to ≤ 12 days) and lesions targeted with I-SBRT will thus be alternated each day to accommodate for the 48 hour interval between fractions.

Patients randomized to arm 2 will start letrozole alone, and add palbociclib on day 21, after completion of I-SBRT. They will undergo tumor Immunogenic-SBRT(I-SBRT) days 1-12 (+/-2 days, to enable inclusion of holidays). During the week preceding day 1, they will undergo simulation and planning for radiotherapy. Each oligometastatic lesion will be treated with I-SBRT every 48 hours. Treatment may be given daily (to keep the total I-SBRT treatment time to ≤ 12 days) and lesions targeted with I-SBRT will thus be alternated each day to accommodate for the 48 hour interval between fractions

Stereotactic Body Radiation Therapy (SBRT) (50GY in 5 fractions)

All patients start standard therapy with oral letrozole (Femara), day 1 of the study.

Letrozole 2.5Mg Tab

Patients randomized to arm 2 will start letrozole alone, and add palbociclib on day 21, after completion of I-SBRT.

Palbociclib 125mg

Lhaden Tshering, B.S.

Pragya Yadav, Ph.D.

Sharanya Chandrasekhar

Silvia Formenti, M.D.

Sharanya Chandrasekhar, M.S.

Hani Ashamalla, M.D.

Hina Ali, M.D.

Akkamma Ravi, M.D.

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.

Combined Immunotherapies in Metastatic ER+ Breast Cancer

CIMER: Combined Immunotherapies in Metastatic ER+ Breast Cancer

Progression free survival (PFS) is defined as the time from the start of study treatment until the disease progression or death.

Serial levels ctDNA can be an early indication of progression

Circulating tumor DNA (ctDNA) levels will be measured to determine baseline cancer heterogeneity and its response to treatment

ORR is defined as the percentage of subjects with either a confirmed complete response (CR) or partial response (PR).

OS is defined as the time from the start of treatment until death.

Adverse events will be collected from patients based on CTCAE version 5.0.

Spots Global Cancer Trial Database for stereotactic body radiation therapy (sbrt) (50gy in 5 fractions)