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

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.

SUBMITTER: Jacot W 

PROVIDER: S-EPMC6854749 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature