Efficacy of Lapatinib in Patients with HER2-Negative Metastatic Breast Cancer and HER2-Positive Circulating Tumor Cells - The DETECT III Clinical Trial

Fehm T, Mueller V, Banys-Paluchowski M, Fasching P, Friedl TW, Hartkopf A, Huober J, Löhberg C, Rack B, Riethdorf S, Schneeweiss A, Wallwiener D, Meier-Stiegen F, Krawczyk N, Jaeger B, Reinhardt F, Hoffmann O, Mueller L, Wimberger P, Ruckhaeberle E, Blohmer JU, Cieslik JP, Franken A, Niederacher D, Neubauer H, Pantel K, Janni W (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Clinical Chemistry American Association for Clinical Chemistry

Book Volume: 70

Pages Range: 307-318

Journal Issue: 1

DOI: 10.1093/clinchem/hvad144

Abstract

Background: The phenotypes of tumor cells change during disease progression, but invasive rebiopsies of metastatic lesions are not always feasible. Here we aimed to determine whether initially HER2-negative metastatic breast cancer (MBC) patients with HER2-positive circulating tumor cells (CTCs) benefit from a HER2-targeted therapy. Methods: The open-label, interventional randomized phase III clinical trial (EudraCT Number 2010-024238-46, CliniclTrials.gov Identifier: NCT01619111) recruited from March 2012 until September 2019 with a follow-up duration of 19.5 months. It was a multicenter clinical trial with 94 participating German study centers. A total of 2137 patients with HER2-negative MBC were screened for HER2-positive CTCs with a final modified intention-to-treat population of 101 patients. Eligible patients were randomized to standard therapy with or without lapatinib. Primary study endpoints included CTC clearance (no CTCs at the end of treatment) and secondary endpoints were progression-free survival, overall survival (OS), and safety. Results: In both treatment arms CTC clearance at first follow-up visit - although not being significantly different for both arms at any time point - was significantly associated with improved OS (42.4 vs 14.1 months; P = 0.002). Patients treated additionally with lapatinib had a significantly improved OS over patients receiving standard treatment (20.5 vs 9.1 months, P = 0.009). Conclusions: DETECT III is the first clinical study indicating that phenotyping of CTCs might have clinical utility for stratification of MBC cancer patients to HER2-targeting therapies. The OS benefit could be related to lapatinib, but further studies are required to prove this clinical observation. ClinicalTrials.gov Registration Number: NCT01619111.

Authors with CRIS profile

Peter Fasching Professur für Translationale Frauenheilkunde und Geburtshilfe Christian Löhberg Department of Obstetrics and Gynaecology

Involved external institutions

Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Heinrich-Heine-Universität Düsseldorf DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Eberhard Karls Universität Tübingen DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE) Universitätsklinikum Essen DE Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE)

How to cite

APA:

Fehm, T., Mueller, V., Banys-Paluchowski, M., Fasching, P., Friedl, T.W., Hartkopf, A.,... Janni, W. (2024). Efficacy of Lapatinib in Patients with HER2-Negative Metastatic Breast Cancer and HER2-Positive Circulating Tumor Cells - The DETECT III Clinical Trial. Clinical Chemistry, 70(1), 307-318. https://dx.doi.org/10.1093/clinchem/hvad144

MLA:

Fehm, Tanja, et al. "Efficacy of Lapatinib in Patients with HER2-Negative Metastatic Breast Cancer and HER2-Positive Circulating Tumor Cells - The DETECT III Clinical Trial." Clinical Chemistry 70.1 (2024): 307-318.

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