OFSET Clinical Trial for Early-Stage Breast Cancer

Overview: The OFSET (Evaluating the Addition of Adjuvant Chemotherapy to Ovarian Function Suppression Plus Endocrine Therapy in Premenopausal Patients With pN0-1, ER-Positive/​HER2-Negative Breast Cancer and an Oncotype Recurrence Score Less Than or Equal to 25) trial is studying whether early-stage, estrogen receptor-positive, HER2-negative breast cancer is less likely to return after treatment in premenopausal women if chemotherapy is added to the usual treatment of hormonal therapy (with an aromatase inhibitor) and ovarian function suppression (using either ovarian suppression medicine or surgical removal of both ovaries).  

Phase: Phase III; Phase III trials compare the safety and effectiveness of a new treatment to the current standard of care. Phase III trials are usually large – some involve thousands of people – and are done at many places in the United States and around the world. 

Number of people to enroll: 3,960

ClinicalTrials.gov ID number: NCT05879926

Sponsor of the trial: NRG Oncology

Collaborator: National Cancer Institute (NCI)

The OFSET trial is enrolling premenopausal women who have been diagnosed with early-stage, estrogen receptor-positive, HER2-negative breast cancer. The cancer must have an Oncotype DX Recurrence Score of 25 or less if any of the axillary lymph nodes contained cancer, or between 16 and 25 if none of the axillary lymph nodes contained cancer. 

The Oncotype DX Breast Recurrence Score Test is a genomic test. It analyzes a sample of a cancer tumor to see how active 21 specific genes are. The activity levels of these genes affect how the cancer behaves, including how likely it is to grow and spread. Genomic tests are used to help make decisions about whether more treatments after surgery could be beneficial.

The trial is designed to see whether adding chemotherapy to the usual treatment – hormonal therapy (with an aromatase inhibitor) and ovarian function suppression (using either ovarian suppression medicine or surgical removal of both ovaries) – reduces the risk of recurrence and improves disease-free survival in premenopausal women with early-stage, estrogen receptor-positive, HER2-negative breast cancer who have a high risk of recurrence.

In the study, people will be randomly assigned to one of two groups:

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  One group will take an aromatase inhibitor (Arimidex, Aromasin, or Femara) for five years and an ovarian suppression medicine (such as Zoladex, Lupron, or Trelstar) every one to three months for five years. People in this group can choose to have surgery to remove both ovaries instead of taking the ovarian suppression medicine.

• Sponsor Message

  The second group will receive chemotherapy that the investigator chooses. Following that, they will take an aromatase inhibitor (Arimidex, Aromasin, or Femara) for five years and an ovarian suppression medicine (such as Zoladex, Lupron, or Trelstar) every one to three months for five years. People in this group can choose to have surgery to remove both ovaries instead of taking the ovarian suppression medicine.

The aromatase inhibitor is taken as a pill once a day. The ovarian suppression medicine is given as an injection, either once a month or once every three months. 

Adult women are eligible for the OFSET study if they:

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  have been diagnosed with early-stage, estrogen receptor-positive, HER2-negative breast cancer

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  are premenopausal 

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  have had surgery for breast cancer and have had a sentinel lymph node biopsy, targeted axillary dissection, or axillary lymph node dissection 

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  have had an Oncotype DX Recurrence Score Test of the breast tumor and got a score of 25 or less if any of their axillary lymph nodes contained cancer, or a score between 16 and 25 if none of their axillary lymph nodes contained cancer 

Learn about the additional eligibility requirements.  

People are not eligible for the OFSET study if they:

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  have been diagnosed with metastatic breast cancer

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  are pregnant or breastfeeding

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  have certain lab test results, such as a platelet count of less than 100,000/mm3, a hemoglobin level of less than 10 g/dL, or an ANC (absolute neutrophil count) of less than 1,200/mm3

Learn about the additional exclusion criteria.

The specific chemotherapy medicine(s) prescribed as part of this study will be chosen by the investigator(s). 

Read about possible side effects for each chemotherapy medicine.

Read about possible side effects for Arimidex (chemical name: anastrozole), Aromasin (chemical name: exemestane), and Femara (chemical name: letrozole).

Read about possible side effects for Zoladex (chemical name goserelin), Lupron (chemical name: leuprolide), and Trelstar (chemical name: triptorelin).

The OFSET study is being conducted at dozens of sites across the United States. 

Call Judy Langer, MD, MS, at 412-339-5300 or email langerj@nrgoncology.org.