TEODOR Trial Launches to Test Personalized Neoadjuvant Therapy for Early-Stage Breast Cancer
核心洞察
The TEODOR trial is investigating whether circulating tumor DNA testing and endocrine responsiveness can guide treatment decisions to replace chemotherapy with endocrine therapy in hormone receptor-positive, HER2 (搜索)-negative breast cancer patients.
The phase 2 randomized controlled trial will enroll approximately 250 patients across 15 sites in Austria, using Natera's Signatera (搜索) ctDNA test to identify patients who may safely avoid neoadjuvant chemotherapy.
Previous studies showed patients testing Signatera (搜索)-negative at diagnosis have excellent outcomes with less than 5% risk of recurrence, suggesting potential for treatment de-escalation.
The Austrian Breast & Colorectal Cancer Study Group (ABCSG) has launched the TEODOR trial, a phase 2 randomized controlled trial investigating whether circulating tumor DNA (ctDNA) testing combined with endocrine responsiveness can guide personalized neoadjuvant therapy decisions for women with hormone receptor-positive (HR+), HER2 (搜索)-negative breast cancer. The study aims to identify patients who may safely forgo chemotherapy in favor of less toxic endocrine therapy.
Trial Design and Patient Population
The multicenter trial (NCT07084558) will enroll approximately 250 patients across 15 sites in Austria through a collaboration between ABCSG and Natera, the company that developed the personalized ctDNA test Signatera (搜索). The study targets women with early-stage HR+/HER2 (搜索)-negative breast cancer who demonstrate specific molecular characteristics.
The trial's protocol begins with a 4-week course of endocrine therapy. Following this initial period, patients who remain ctDNA-negative using the Signatera (搜索) test and demonstrate favorable endocrine sensitivity—as measured by the Ki-67 (搜索) proliferation index—will be randomized into two treatment arms. One arm will continue with additional endocrine therapy, while the other will proceed with standard chemotherapy.
Scientific Rationale
The TEODOR trial builds on previous studies demonstrating excellent outcomes for patients who test Signatera (搜索)-negative at diagnosis and subsequently receive chemotherapy, with these patients showing a risk of recurrence of less than 5%. This favorable prognosis group represents an opportunity for treatment de-escalation to avoid the significant short- and long-term side effects associated with chemotherapy.
"TEODOR is designed to examine whether we can use endocrine responsiveness and ctDNA status to optimize systemic therapy in the neoadjuvant setting," said ABCSG president Michael Gnant, MD, FACS, FEBS, professor of surgery at the Comprehensive Cancer Center, Medical University of Vienna, and principal investigator of the TEODOR trial. "This study marks a critical step toward more personalized medicine, leveraging the latest technologies to improve patient care."
Primary and Secondary Endpoints
The primary endpoint of the TEODOR trial is the rate of neoadjuvant therapy response, assessed using both pathological complete response (pCR) and the modified Preoperative Endocrine Prognostic Index (PEPI) score. These established metrics will enable direct comparison of efficacy between the endocrine therapy and chemotherapy arms in the preselected patient population.
Secondary endpoints include critical long-term outcomes such as breast cancer recurrence and overall survival, which are essential for confirming the durability and safety of the endocrine-only approach.
Clinical Implications
The potential for a significant portion of patients with early-stage HR+/HER2 (搜索)-negative breast cancer to avoid chemotherapy would represent a major clinical advancement. An endocrine therapy-only approach could improve quality of life during treatment by reducing side effects such as nausea, hair loss, and the risk of long-term complications like cardiotoxicity or neuropathy.
"With the TEODOR trial, our goal is to identify patients who may be able to safely forgo chemotherapy," said Angel Rodriguez, MD, medical director of oncology at Natera. "We are proud to collaborate with ABCSG on this important trial, and we hope this study will support the role of Signatera (搜索) in guiding neoadjuvant therapy in breast cancer."
The trial reflects the growing trend in oncology toward personalized medicine approaches that use molecular and biological markers to stratify patients and tailor therapies to maximize efficacy while minimizing toxicity.