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Therapeutic intervention based on circulating tumor cell phenotype in metastatic breast cancer: concept of the DETECT study program

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Abstract

Purpose

The aim of the ongoing DETECT study program is to evaluate therapeutic intervention based on phenotypes of circulating tumor cells (CTC) in patients with metastatic breast cancer (MBC). Currently (as of July 2015) more than half of the projected about 2000 patients with MBC have already been screened for CTC.

Methods

Women with HER2-negative primary tumor and presence of CTC are recruited into different DETECT trials according to the HER2-phenotype of CTC. Patients with HER2-positive CTC are randomized to treatment with physicians’ choice therapy (standard chemo- or endocrine therapy) with or without additional HER2-targeted therapy with lapatinib in the DETECT III trial. In DETECT IVa, postmenopausal patients with hormone-receptor positive primary cancer and HER2-negative CTC receive everolimus and standard endocrine therapy. For women with HER2-negative CTC and triple negative MBC or hormone-receptor positive tumor and indication for chemotherapy, a treatment with eribulin is offered (DETECT IVb). The clinical efficacy is investigated by CTC-Clearance and progression-free survival (PFS). The DETECT V/CHEVENDO trial extends the DETECT study program for women with HER2-positive and hormone-receptor positive MBC. The primary objective of this trial is to compare safety and quality of life (QoL) as assessed by the occurrence of adverse events in patients treated with dual (trastuzumab plus pertuzumab) HER2-targeted therapy plus either endocrine or chemotherapy. The translational research projects of the DETECT study program focus on further molecular characterization of CTC and evaluation of markers for their suitability to predict treatment response and to facilitate the development of more personalized treatment options.

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Acknowledgments

We thank all the patients for participating at this study and donating their blood samples for research purposes. We also thank Anke Faul and especially Evelyn Jäckel for their excellent support. The DETECT study program is supported by the Investigator-Initiated Study Program of Janssen Diagnostics. The clinical trials are also supported by GlaxoSmithKline GmbH & Co. KG, Pierre Fabre Pharma GmbH, TEVA GmbH, AMGEN GmbH, Novartis Pharma GmbH, Eisai GmbH and Roche Pharma AG. The study medication is provided free of charge by GlaxoSmithKline GmbH & Co. KG (Lapatinib), Pierre Fabre Pharma GmbH (Navelbine oral), TEVA GmbH (non-pegylated liposomal doxorubicin NPLD), Novartis Pharma GmbH (Everolimus), Eisai GmbH (Eribulin) and Roche (Pertuzumab).

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Authors and Affiliations

  1. Gynecology and Obstetrics, University Hospital Ulm, Prittwitzstraße 43, 89075, Ulm, Germany

    Amelie Schramm, Thomas W. P. Friedl, Fabienne Schochter, Christoph Scholz, Nikolaus de Gregorio, Jens Huober & Wolfgang Janni

  2. Gynecology and Obstetrics, Hospital of Ludwig-Maximilians-University, Munich, Germany

    Brigitte Rack, Elisabeth Trapp & Marianna Alunni-Fabbroni

  3. Gynecology, University Hospital Hamburg-Eppendorf, Hamburg, Germany

    Volkmar Müller

  4. National Center for Tumor Diseases and Department of Gynecology and Obstetrics, University Hospital Heidelberg, Heidelberg, Germany

    Andreas Schneeweiss

  5. Department of Tumor Biology, University Hospital Hamburg-Eppendorf, Hamburg, Germany

    Klaus Pantel

  6. Gynecology and Obstetrics, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany

    Franziska Meier-Stiegen & Tanja Fehm

  7. Gynecology and Obstetrics, University Hospital Tuebingen, Tuebingen, Germany

    Andreas Hartkopf, Florin-Andrei Taran & Diethelm Wallwiener

Authors
  1. Amelie Schramm
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  2. Thomas W. P. Friedl
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  10. Volkmar Müller
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  11. Andreas Schneeweiss
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  13. Franziska Meier-Stiegen
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  16. Diethelm Wallwiener
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  17. Wolfgang Janni
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  18. Tanja Fehm
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Corresponding author

Correspondence to Amelie Schramm.

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Conflict of interest

Prof. T. Fehm and her project are funded by Novartis Research grant. Prof. Janni receives Research Grant and Honoraria from Janssen Diagnostic as well as support for the DETECT study concept by the listed companies below. PD Dr. Brigitte Rack is supported by Janssen Diagnostics. The other authors confirm that this article content has no conflict of interest.

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Schramm, A., Friedl, T.W.P., Schochter, F. et al. Therapeutic intervention based on circulating tumor cell phenotype in metastatic breast cancer: concept of the DETECT study program. Arch Gynecol Obstet 293, 271–281 (2016). https://doi.org/10.1007/s00404-015-3879-7

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  • DOI: https://doi.org/10.1007/s00404-015-3879-7

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