Efficacy of Lapatinib in Patients with HER2-Negative Metastatic Breast Cancer and HER2-Positive Circulating Tumor Cells-The DETECT III Clinical Trial
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Efficacy of Lapatinib in Patients with HER2-Negative Metastatic Breast Cancer and HER2-Positive Circulating Tumor Cells-The DETECT III Clinical Trial. / Fehm, Tanja; Mueller, Volkmar; Banys-Paluchowski, Maggie; Fasching, Peter A; Friedl, Thomas W P; Hartkopf, Andreas; Huober, Jens; Loehberg, Christian; Rack, Brigitte; Riethdorf, Sabine; Schneeweiss, Andreas; Wallwiener, Diethelm; Meier-Stiegen, Franziska; Krawczyk, Natalia; Jaeger, Bernadette; Reinhardt, Florian; Hoffmann, Oliver; Mueller, Lothar; Wimberger, Pauline; Ruckhaeberle, Eugen; Blohmer, Jens-Uwe; Cieslik, Jan-Philipp; Franken, André; Niederacher, Dieter; Neubauer, Hans; Pantel, Klaus; Janni, Wolfgang; DETECT Study Group.
in: CLIN CHEM, Jahrgang 70, Nr. 1, 04.01.2024, S. 307-318.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Efficacy of Lapatinib in Patients with HER2-Negative Metastatic Breast Cancer and HER2-Positive Circulating Tumor Cells-The DETECT III Clinical Trial
AU - Fehm, Tanja
AU - Mueller, Volkmar
AU - Banys-Paluchowski, Maggie
AU - Fasching, Peter A
AU - Friedl, Thomas W P
AU - Hartkopf, Andreas
AU - Huober, Jens
AU - Loehberg, Christian
AU - Rack, Brigitte
AU - Riethdorf, Sabine
AU - Schneeweiss, Andreas
AU - Wallwiener, Diethelm
AU - Meier-Stiegen, Franziska
AU - Krawczyk, Natalia
AU - Jaeger, Bernadette
AU - Reinhardt, Florian
AU - Hoffmann, Oliver
AU - Mueller, Lothar
AU - Wimberger, Pauline
AU - Ruckhaeberle, Eugen
AU - Blohmer, Jens-Uwe
AU - Cieslik, Jan-Philipp
AU - Franken, André
AU - Niederacher, Dieter
AU - Neubauer, Hans
AU - Pantel, Klaus
AU - Janni, Wolfgang
AU - DETECT Study Group
N1 - © Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2024/1/4
Y1 - 2024/1/4
N2 - 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.
AB - 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.
KW - Female
KW - Humans
KW - Breast Neoplasms/drug therapy
KW - Disease Progression
KW - Kinetics
KW - Neoplastic Cells, Circulating
U2 - 10.1093/clinchem/hvad144
DO - 10.1093/clinchem/hvad144
M3 - SCORING: Journal article
C2 - 38175595
VL - 70
SP - 307
EP - 318
JO - CLIN CHEM
JF - CLIN CHEM
SN - 0009-9147
IS - 1
ER -
