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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • University Hospital Duesseldorf
  • University Hospital Hamburg Eppendorf
  • Universitätsklinikum Schleswig-Holstein - Campus Lübeck
  • State Vocational Colleges at the University Hospital Erlangen
  • Ulm University Medical Center
  • University Hospital Tübingen
  • German Cancer Research Center (DKFZ)
  • University Hospital Essen
  • Onkologische Schwerpunktpraxis Leer
  • Charité – Universitätsmedizin Berlin

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.

Details

Original languageEnglish
Pages (from-to)307-318
Number of pages12
JournalClinical chemistry
Volume70
Issue number1
Publication statusPublished - 4 Jan 2024
Peer-reviewedYes

External IDs

Scopus 85181771850

Keywords

Sustainable Development Goals

Keywords

  • Female, Humans, Breast Neoplasms/drug therapy, Disease Progression, Kinetics, Neoplastic Cells, Circulating