Personalized Detection of ctDNA for Patients With HER2-Positive Metastatic Breast Cancer Who Achieved Durable Response by Anti-HER2 Treatment
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Sponsor
- Nagoya City University
- Enrollment
- 50
- Locations
- 8
- Primary Endpoint
- The status of ctDNA
Study Overview
Brief Summary
Anti-HER2 therapy, such as trastuzumab and pertuzumab, has significantly improved long-term survival in HER2-positive breast cancer. The updated data of the CLEOPATRA trial showed significant Kaplan-Meier curves, suggesting the potential for a cure. However, the efficacy of maintenance therapy in long-term responders remains unexplored. This study will assess MRD in unresectable HER2-positive breast cancer cases with long-term response using the Signatera™ ctDNA assay, which could contribute to future treatment strategy development.
Detailed Description
More than 20 years have passed since the introduction of trastuzumab as a treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The additive effect of trastuzumab, an anti-HER2 antibody, was evaluated in combination with chemotherapy (paclitaxel or anthracycline plus cyclophosphamide) in previously untreated, unresectable HER2-positive breast cancer. The number of cases achieving long-term survival with anti-HER2 therapy has been increasing, and this trend is also observed in our institution.
The treatment for unresectable breast cancer is systemic therapy, which is typically continued as long as it remains effective and side effects are tolerable. However, in cases of long-term response in HER2-positive breast cancer, the impact of continuing anti-HER2 therapy alone as maintenance therapy on prognosis and the safety of treatment discontinuation remains unclear.
In recent years, the clinical application of circulating tumor DNA (ctDNA) has attracted attention for early diagnosis and detection of minimal residual disease. Signatera™, an assay developed by Natera Inc., detects minimal residual disease. It is a personalized ctDNA test for individual patients, and a study targeting breast cancer patients post-surgery reported a detection sensitivity exceeding 90% for variant allele frequencies (VAF) as low as 0.01%. This high sensitivity has been reported not only in breast cancer but also in other cancer types. However, there have been no reports of Signatera analysis in unresectable breast cancer.
In this study, investigators will use Signatera™ to evaluate and analyze ctDNA status (ctDNA positive or negative) in cases of unresectable HER2-positive breast cancer that have achieved long-term response. By assessing ctDNA in such cases, this study may lead to new therapeutic strategies, such as de-escalating anti-HER2 therapy in ctDNA-negative cases.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 20 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •HER2 + metastatic breast cancer
- •Pre / post menopausal
- •Previously treated with anti-HER2 therapy
- •Continuing CR or PR for more than 2 year
Exclusion Criteria
- •Patients who were deemed inappropriate as research subjects based on the physician's judgment, such as those possibly receiving inappropriate treatment.
Arms & Interventions
Continuing anti-HER2 treatment
Breast cancer patients who are continuing complete response (CR) or partial response (PR) for more than two years of anti-HER2 treatment (trastuzumab, pertuzumab, T-DM1, and T-DXd)
Intervention: SIgnatera (Diagnostic Test)
Follow up (stop anti-HER2 treatment)
Breast cancer patients who stopped anti-HER2 treatment with complete response (CR) or partial response (PR) after more than two years of anti-HER2 treatment(trastuzumab, pertuzumab, T-DM1, and T-DXd)
Intervention: SIgnatera (Diagnostic Test)
Continuing anti-HER2 treatment
Breast cancer patients who are continuing complete response (CR) or partial response (PR) for more than two years of anti-HER2 treatment (trastuzumab, pertuzumab, T-DM1, and T-DXd)
Intervention: Trastuzumab (Herceptin) (Drug)
Outcomes
Primary Outcomes
The status of ctDNA
Time Frame: 1 year
To assess the status of ctDNA in CR patients with/without continuing treatment, or PR patients with continuing treatment
Secondary Outcomes
No secondary outcomes reported
Investigators
Kazuki Nozawa
MD
Nagoya City University