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Clinical Trial
. 2019 Nov 14;21(1):121.
doi: 10.1186/s13058-019-1215-z.

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

William Jacot  1   2   3 , Paul Cottu  4 , Frederique Berger  5 , Coraline Dubot  4 , Laurence Venat-Bouvet  6 , Alain Lortholary  7 , Hugues Bourgeois  8 , Marc Bollet  9 , Veronique Servent  10 , Elisabeth Luporsi  11 , Marc Espié  12 , Severine Guiu  1   2 , Veronique D'Hondt  1   2 , Veronique Dieras  4 , Marie-Paule Sablin  4 , Etienne Brain  4 , Souhir Neffati  5 , Jean-Yves Pierga  4   13   14 , Francois-Clement Bidard  15   16   17
Affiliations
Clinical Trial

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

William Jacot et al. Breast Cancer Res. .

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 a HER2/CEP17 ratio of ≥ 2.2 by fluorescent in situ hybridization (CellSearch) were considered to be HER2-amplified (HER2amp). Patients with ≥ 1 HER2amp CTC 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 in N = 118 (78.7%) and N = 86 (57.3%) patients, respectively. ≥1 HER2amp CTC 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 with HER2 amplification 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.

Keywords: Circulating tumor cells; HER2; Liquid biopsy; Metastatic breast cancer; Trastuzumab-emtansine.

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Conflict of interest statement

WJ: honoraria and travel grants from Roche. PC: research support from Roche. FCB and JYP: research support from Janssen Diagnostics, research support, honoraria, and travel grants from Roche. The other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart
Fig. 2
Fig. 2
Correlations between absolute CTC count and downstream CTC characterization. a Correlation between the number of CTC detected and the number of CTC with interpretable FISH results. b Correlation, in the 14 patients with ≥ 1 HER2amp CTC at the screening step, between the number of (i) CTC, (ii) CTC with interpretable FISH result, and (iii) HER2amp CTC. b Correlation between the number of CTC detected and the number of JER2amp CTC for the 14 patients with ≥ 1 HERamp CTC detected. For each patient, the number of CTC with interpretable FISH results is shown in brackets.
Fig. 3
Fig. 3
Survival curves. Progression-free survival (a) and overall survival (b) for patients with ≥ 1 HER2amp CTC treated with T-DM1 (in yellow) and patients with ≥ 1 CTC but no HER2amp CTC, treated per standard of care (in black)
See this image and copyright information in PMC

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