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Actionability of HER2-amplified circulating tumor cells in HER2-negative metastatic breast cancer: the CirCe T-DM1 trial

1 Dec 2019Breast Cancer Research

DOI : 10.1186/s13058-019-1215-z

Authors

William Jacot, Paul Cottu, Frederique Berger, Coraline Dubot, Laurence Venat-Bouvet, Alain Lortholary, Hugues Bourgeois, Marc Bollet, Veronique Servent, Elisabeth Luporsi, Marc Espié, Severine Guiu, Veronique D’Hondt, Veronique Dieras, Marie-Paule Sablin, Etienne Brain, Souhir Neffati, Jean-Yves Pierga, Francois-Clement Bidard

Abstract

Abstract

Background

In this prospective phase 2 trial, we assessed the efficacy of trastuzumab-emtansine (T-DM1) in HER2-negative metastatic breast cancer (MBC) patients with HER2-positive CTC.

Methods

Main inclusion criteria for screening were as follows: women with HER2-negative MBC treated with ≥ 2 prior lines of chemotherapy and measurable disease. CTC with aHER2/CEP17 ratio of ≥ 2.2 by fluorescent in situ hybridization (CellSearch) were considered to beHER2-amplified (HER2amp). Patients with ≥ 1HER2ampCTC were eligible for the treatment phase (T-DM1 monotherapy). The primary endpoint was the overall response rate.

Results

In 154 screened patients, ≥ 1 and ≥ 5 CTC/7.5 ml of blood were detected inN = 118 (78.7%) andN = 86 (57.3%) patients, respectively. ≥1HER2ampCTC was found in 14 patients (9.1% of patients with ≥ 1 CTC/7.5 ml). Among 11 patients treated with T-DM1, one achieved a confirmed partial response. Four patients had a stable disease as best response. Median PFS was 4.8 months while median OS was 9.5 months.

Conclusions

CTC withHER2amplification can be detected in a limited subset of HER2-negative MBC patients. Treatment with T-DM1 achieved a partial response in only one patient.

Trial registration

NCT01975142, Registered 03 November 2013