The first patient with metastatic human epidermal growth factor receptor 2-positive (HER2+) breast cancer has been enrolled in the HEROES clinical trial exploring the discontinuation or de-escalation of anti-HER2-targeted therapy.
“The HEROES study could significantly reshape the way oncologists treat patients with metastatic HER2+ breast cancer,” Dr. Thibault de la Motte Rouge, principal investigator of the trial and medical oncologist at the Comprehensive Cancer Centre Eugène Marquis in Rennes, France, where he currently holds the position of research director, said in a release from Natera, Inc. “This could also pave the way for future research into [circulating tumor] DNA-guided treatment de-escalation in breast cancer.”
The HEROES trial aims to enroll about 170 patients with metastatic HER2+ breast cancer who have stopped anti-HER2 maintenance therapy. The study’s primary end goal is one-year progression-free survival in the Signatera-negative group. Researchers will also examine circulating tumor DNA dynamics and quality-of-life outcomes to assess the feasibility of circulating tumor DNA-guided treatment de-escalation in patients without detectable molecular disease.
Signatera is a tumor-informed molecular residual disease test that detects circulating tumor DNA to identify recurrence and guide treatment. Available for clinical and research use, it is covered by Medicare for select cancers and immunotherapy monitoring. Clinically validated across multiple cancers, it has over 100 peer-reviewed studies.
The HEROES trial marks Natera’s first clinical trial that uses Signatera to guide de-escalation of therapy in patients with metastatic HER2+ breast cancer, as per the release.
The trial is funded by the French Ministry of Health through the Hospital Clinical Research Program and sponsored by Unicancer. It is being developed within Unicancer’s French Breast Cancer Intergroup network.
“We are excited to see the first patients enrolled in the HEROES clinical trial,” Dr. Angel Rodriguez, senior medical director of oncology at Natera, said in the release. “Safely discontinuing treatment has been a long-lasting dilemma in HER2 metastatic breast cancer. With Signatera monitoring, we hope oncologists can identify the patients without detectable disease who may be able to avoid additional therapy that can be costly and potentially harmful to their care.”
At baseline, all patients enrolled are receiving standard-of-care anti-HER2 targeted therapies and have been on treatment for at least two years. Patients who test Signatera-negative at baseline will discontinue treatment and be monitored with serial Signatera testing and diagnostic imaging. If radiological progression is confirmed or a patient becomes Signatera-positive at any point during the trial, prior therapy will be resumed, or a new treatment will be initiated. Patients who are Signatera-positive at baseline will continue maintenance therapy and will not proceed in the trial.
HER2 is a protein in cancer cells that can drive rapid tumor growth when overexpressed, according to the release. HER2-positive breast cancer accounts for 15% to 20% of cases. Standard maintenance treatment includes anti-HER2 therapies, often requiring lifelong use.
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