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Interception of molecular relapse in breast cancer: The SURVIVE HERoes study (NCT06643585).

Janni W, Friedl TW, Huesmann ST, Rack B, Heublein S, Schäffler H, Mehmeti F, Saup R, Fink A, Braun T, Fehm TN, Mueller V, Wiesmueller LM, Pantel K, Hartkopf AD, Hussong M, Chevalier A, Fasching P, Pfister K (2026)

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Publication Type: Journal article

Publication year: 2026

Journal

Book Volume: 44

Journal Issue: 16

DOI: 10.1200/JCO.2026.44.16_suppl.TPS646

Abstract

TPS646Background: Current research on circulating tumor DNA (ctDNA) in the adjuvant setting of early breast cancer (eBC) demonstrates its strong prognostic significance. Patients who are ctDNA-positive in the absence of radiological evidence of disease recurrence (i.e., molecular relapse) have significantly reduced disease-free and overall survival. Secondary adjuvant intervention trials employing highly potent therapeutic agents represent an innovative and promising strategy to intercept disease recurrence at the molecular stage. Methods: SURVIVE HERoes is a phase III, randomized clinical trial comparing the antibody–drug conjugate trastuzumab deruxtecan (T-DXd) with standard of care (SoC) in patients with molecular residual or recurrent disease. Eligible patients must have a positive circulating tumor DNA (ctDNA) result detected using a tumor-informed assay (RaDaR), while staging examinations show no evidence of residual or recurrent disease. Participants must have HER2-positive, HER2-low, or—following an approved study amendment—HER2-ultralow early breast cancer (eBC), irrespective of hormone receptor (HR) status, and must have completed primary therapy, including surgery with R0 resection, with or without chemotherapy and/or radiotherapy. 180 participants are randomized in a 2:1 ratio to receive T-DXd (+ endocrine therapy for HR positive patients) or standard of care for 48 weeks, followed by a 48-week follow-up phase. Stratification factors include hormonal receptor status (positive versus negative) and HER2-status (positive versus low versus ultralow). Staging examinations and ctDNA assessments will be performed every 12 weeks during the 2-year study phase per patient. The study is accompanied by a comprehensive translational research program. The primary endpoint is the ctDNA clearance rate after 48 weeks, comparing participants in the experimental arm (receiving T-DXd) with those in the control arm (receiving standard of care), irrespective of ctDNA test results at other time points. Secondary endpoints include invasive disease-free survival, overall survival, ctDNA clearance at other time points, safety, and quality of life (QoL), as assessed by EORTC QLQ-C30 and PA-F12. Recruitment: Recruitment began in Q2/2025 and is anticipated to continue until 2030. Fifty sites across Germany are planned for participation. Discussion: Treating ctDNA-positive patients without radiographic evidence of recurrence is a novel therapeutic strategy. If SURVIVE HERoes and similar studies targeting molecular relapse yield positive results, they could pave the way for a new molecularly driven personalized surveillance and treatment approach. Clinical trial information: NCT06643585.

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How to cite

APA:

Janni, W., Friedl, T.W., Huesmann, S.T., Rack, B., Heublein, S., Schäffler, H.,... Pfister, K. (2026). Interception of molecular relapse in breast cancer: The SURVIVE HERoes study (NCT06643585). Journal of Clinical Oncology, 44(16). https://doi.org/10.1200/JCO.2026.44.16_suppl.TPS646

MLA:

Janni, Wolfgang, et al. "Interception of molecular relapse in breast cancer: The SURVIVE HERoes study (NCT06643585)." Journal of Clinical Oncology 44.16 (2026).

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