Adding Surgery and Radiation to the Usual Treatment for HER2-Positive Breast Cancer That Had Already Spread at Diagnosis

Summary

This phase III trial evaluates the effect of adding locoregional therapy (surgery and radiation) and metastasis-directed stereotactic body radiation therapy (SBRT) to standard systemic therapy following standard HER2-targeted systemic therapy, compared to standard systemic therapy alone, in treating patients with HER2-positive stage IV breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or to a limited number of sites (oligometastatic). The usual approach for patients with (oligo)metastatic HER2-positive breast cancer is systemic drug treatment, which means medicines that travel through the whole body to treat both the breast and any areas where the cancer has spread. There are a number of approved HER2-targeted systemic therapy regimens available to patients. These typically include immunotherapy and/or chemotherapy. Immunotherapy drugs may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Unlike systemic therapy, locoregional therapies like surgery and radiation are focused treatments at the site of disease, delivered with the intent of sparing healthy tissues. Breast surgeries such as breast conserving therapy or total mastectomy are procedures in which the cancerous breast tissue (and healthy breast tissue in the case of total mastectomy) are surgically removed from the body. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Adding locoregional therapy, as well as metastasis-directed SBRT, to standard systemic therapy may help patients with (oligo)metastatic, HER2-positive stage IV breast cancer live longer overall or before their cancer progresses, and may help more patients achieve no evidence of disease, when compared to standard systemic therapy alone.

Conditions

• Anatomic Stage IV Breast Cancer AJCC v8
• Metastatic HER2-Positive Breast Carcinoma
• Oligometastatic Breast Carcinoma

Interventions

BIOLOGICAL

Trastuzumab Deruxtecan

Given T-DXd

BIOLOGICAL

Trastuzumab Emtansine

Given T-DM1

PROCEDURE

Ultrasound Imaging

Undergo ultrasound

RADIATION

Stereotactic Body Radiation Therapy

Undergo SBRT

RADIATION

Stereotactic Radiosurgery

Undergo SRS/SRT

DRUG

Taxane Compound

Given taxane therapy

PROCEDURE

Total Mastectomy

Undergo total mastectomy

BIOLOGICAL

Trastuzumab

Given trastuzumab

PROCEDURE

Biopsy Procedure

Undergo biopsy

PROCEDURE

Biospecimen Collection

Undergo collection of blood samples

PROCEDURE

Breast Conservation Treatment

Undergo breast conserving therapy

PROCEDURE

Computed Tomography

Undergo CT and/or PET/CT

DRUG

Cyclin-Dependent Kinase 4 Inhibitor

Given CDK4/6 inhibitor

DRUG

Cyclin-Dependent Kinase 6 Inhibitor

Given CDK4/6 inhibitor

PROCEDURE

Echocardiography Test

Undergo ECHO

DRUG

HER2-targeted Therapy

Receive HER2-targeted systemic therapy

DRUG

Hormone Therapy

Given endocrine therapy

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

PROCEDURE

Mammography

Undergo mammography

BIOLOGICAL

Pertuzumab

Given pertuzumab

PROCEDURE

Positron Emission Tomography

Undergo PET/CT

RADIATION

Radiation Boost

Undergo RT boost

RADIATION

Radiation Therapy

Undergo RT

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• SWOG Cancer Research Network

  lead NETWORK

Principal Investigators

• Mariya Rozenblit · SWOG Cancer Research Network

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2027-03-09

Primary Completion

2032-05-31

Completion

2033-05-31