October 17, 2018

Spotlight Trial: ATOP TRIAL: Adjuvant Ado-Trastuzumab Emtansine (T-DM1) for Older Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer

A phase II trial involving Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Massachusetts General Hospital, and other study locations across the country, including Mayo Clinic, City of Hope, and University of North Carolina, led by principal investigator Rachel A. Freedman, MD, MPH (DFCI), has been designed to assess the side effects and benefits of a treatment called T-DM1 (ado-trastuzumab emtansine) in older patients with HER2-positive breast cancer. 

“There are many collaborators coming together for this study, making it a rich resource to answer questions such as what functional changes happen to patients over time and what factors might predict side effects for patients enrolled in the study,” Dr. Freedman said. This study is funded by grants awarded to Dr. Freedman from Gateway for Cancer Research, Susan G. Komen, and the Gloria Spivak Faculty Advancement Fund, as well as past contributions from Genentech. 

T-DM1 is an antibody-drug conjugate composed of trastuzumab (an antibody) linked to DM1 (a cytotoxic chemotherapy drug). T-DM1 is a type of targeted cancer therapy that functions via direct targeting of HER2-positive breast cancer cells, while limiting chemotherapy exposure to healthy cells in the body. 

T-DM1 is currently approved for the treatment of advanced, previously treated, HER2-positive breast cancer. However, T-DM1 has not been approved for the treatment of stage I, II, or III breast cancer. 

A New Treatment for Older Patients

“The main goal is to identify a potential tolerable and efficacious treatment option for older patients with HER2-positive breast cancer,” said Dr. Freedman. “The amount of evidence that we have in past studies with regard to treating older patients with breast cancer is extremely limited, and most of the studies include patients who are much younger or who are in better health, which is not representative of many patients with breast cancer.”

Patients who enroll in the study will receive 1 year of postoperative T-DM1 infusions, and investigators will collect detailed toxicity information in order to better understand how this treatment affects a patient’s quality of life. Patients will be followed for up to 5 years through medical records and annual communications to assess for breast cancer recurrence or any related issues.

The investigators will also evaluate potential biomarkers that may be associated with outcomes in patients treated with T-DM1. Additionally, genomic studies using surgical tissue samples will be conducted to better characterize these HER2-positive tumors. “The genetic underpinnings of tumors in older adults are not well described in the literature and there is a great need to better understand the genetic changes which may be present in HER2-positive tumors in this population and may help predict how a patient may respond to treatment,” Dr. Freedman said.

Dr. Freedman noted that different considerations may be required when treating older patients with breast cancer due to other medical problems, concerns, and priorities. “My hope with this study is that we will … understand whether T-DM1 can emerge as an alternative treatment option in the future, particularly for the older patient who may otherwise not receive treatment for her cancer because of concern that she won’t tolerate it well,” Dr. Freedman said. 

Study Design

A total of 120 patients who are at least 60 years of age and who have had surgery to remove a stage I-III HER2-positive breast cancer will receive intravenous T-DM1 infusions once every 3 weeks for 1 year. The primary outcome is 5-year invasive disease-free survival. Secondary outcomes include toxicity, cardiac-related adverse events, site of first recurrence, and recurrence-free and overall survival.

Phase II Trial

ATOP TRIAL: Adjuvant Ado-Trastuzumab Emtansine (T-DM1) for Older Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer

DF/HCC Principal Investigator: Rachel A. Freedman, MD, MPH (DFCI)

NIH Trial Number: NCT03587740

DF/HCC Protocol Number: 18-124

The trial is recruiting patients. Find more information at ClinicalTrials.gov.

— By Erin M. Burns, PhD, MSPH