Testing the Addition of Chemotherapy to the Usual Treatment of Ovarian Function Suppression plus Hormonal Therapy in Premenopausal ER-Positive/HER2-Negative Breast Cancer Patients Who Are At High Risk of Cancer Returning, OFSET Trial

Summary

Objectives

PRIMARY OBJECTIVE:
I. To determine whether adjuvant chemotherapy (ACT) added to ovarian function suppression (OFS) plus endocrine therapy (ET) is superior to OFS plus ET in improving invasive breast cancer-free survival (IBCFS) among premenopausal, early- stage breast cancer (EBC) patients with estrogen receptor (ER)-positive, HER2-negative tumors and 21-gene recurrence score (RS) between 16-25 (for pN0 patients) and 0-25 (for pN1 patients).

SECONDARY OBJECTIVES:
I. To determine whether ACT added to OFS plus ET is superior to OFS plus ET in improving invasive disease-free survival (IDFS) among premenopausal, EBC patients with ER-positive, HER2-negative tumors and 21-gene RS between 16-25 (for pN0 patients) and 0-25 (for pN1 patients).
II. To determine whether ACT added to OFS plus ET is superior to OFS plus ET in improving overall survival (OS) among premenopausal, EBC patients with ER-positive, HER2-negative tumors and 21-gene RS between 16-25 (for pN0 patients) and 0-25 (for pN1 patients).
III. To determine whether ACT added to OFS plus ET is superior to OFS plus ET in improving distant recurrence-free interval (DRFI) among premenopausal, EBC patients with ER-positive, HER2-negative tumors and 21-gene RS between 16-25 (for pN0 patients) and 0-25 (for pN1 patients).
IV. To determine whether ACT added to OFS plus ET is superior to OFS plus ET in improving breast cancer-free interval (BCFI) among premenopausal, EBC patients with ER-positive, HER2-negative tumors and 21-gene RS between 16-25 (for pN0 patients) and 0-25 (for pN1 patients).
V. To determine whether patients who receive ACT added to OFS plus ET will have more severe menopausal symptoms, measured by the Functional Assessment of Cancer Therapy-Endocrine Symptoms Subscale (FACT ESS)-19 score, compared to those who do not receive ACT.
VI. To determine whether patients who receive ACT added to OFS plus ET will have increased pain during aromatase inhibitor (AI) therapy compared to patients who do not receive ACT.

EXPLORATORY OBJECTIVES:
I. To determine if there are differences in adherence to long-term OFS plus ET by treatment arm assignment.
II. To determine if there are differences in the degree of ovarian suppression between treatment arms.
III. To determine if ACT added to OFS plus ET increases the long-term toxicities of OFS plus ET in premenopausal women with EBC.
IV. To determine whether patients who receive ACT added to OFS plus ET will have similar selected quality of life (QOL) outcomes during OFS plus ET compared to patients who do not receive ACT.
V. To assess if survival outcomes differ by race/ethnicity.
VI. To determine if body mass index (BMI) contributes to outcome in this study population.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: Patients receive a gonadotropin-releasing hormone (GnRH) agonist via injection and an AI orally (PO) per the study investigator's choice. Treatment with AI continues for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients also undergo mammogram or magnetic resonance imaging (MRI) scans during screening and then every 12 months on study and during follow up, and dual X-ray absorptiometry (DEXA) scans every 2 years on study. Patients may also undergo collection of tumor tissue within 90 days after randomization and at time of disease recurrence, and collection of blood samples before randomization, at 12, 24, 36, 48, and 60 months, and at time of disease recurrence.

ARM 2: Patients receive adjuvant chemotherapy regimen, a GnRH agonist via injection, and an AI PO per the study investigator's choice. Treatment with AI continues for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients also undergo mammogram or MRI scans during screening and then every 12 months on study and during follow up, and DEXA scans every 2 years on study. Patients may also undergo collection of tumor tissue within 90 days after randomization and at time of disease recurrence, and collection of blood samples before randomization, at 12, 24, 36, 48, and 60 months, and at time of disease recurrence.

After completion of study treatment, patients are followed every 12 months for 10 years.