Abstract 5522
Background
Changes of HER2 status has been reported in circulating tumor cells (CTC) isolated from preclinical models and metastatic breast cancer (MBC) patients. The prospective multicentric phase II “CirCe T-DM1” trial was set up to assess whether HER2-amplified CTC are detectable in HER2-negative MBC and whether these cancers would respond to anti-HER2 therapy.
Methods
HER2-amplified CTC were screened in HER2-negative (HER2-/ER- and HER2-/ER+) MBC patients starting a 3rd line or 4th line of systemic therapy. CTC were detected by CellSearch® (Janssen Diagnostics) and FISH was performed on isolated CTCs. HER2-amplification was defined by a HER2/CEP17 ratio ≥2.2. Patients with ≥1 HER2-amplified CTC, measurable disease and adequate organ function were eligible. After stratification according to amplified CTC count (< vs ≥ 3), patients received single agent T-DM1. The primary endpoint of the study was the response rate by RECIST criteria.
Results
From 11/2013 to 08/2016, 155 MBC patients were screened. 11 (9.2%) and 3 patients (2.5%) had 1-2 and ≥3 HER2-amplified CTCs respectively (minimal HER2/CEP17 ratio: 2.5). In the 14 patients with HER2-amplified CTC, the fraction of HER2-amplified CTCs among all detected CTCs was low (median 1.6%, range [0.3%-35.3%]), and presence of HER2-amplified CTCs was not associated with any patients’ characteristics. 11 patients were treated with single agent T-DM1. Partial response was confirmed in one patient with 1 HER2-amplified CTC (among 9 CTC detected); median PFS was 4.9 months (range: 1.8-10.1).
Conclusions
This study shows that CTCs with a true HER2-amplification can be detected in advanced HER2-negative MBC, mostly as a minor CTCs subset. Although one confirmed response was observed in our study, the overall low response rate to specific anti-HER2 therapy does not support the clinical utility of such strategy in that setting.
Clinical trial identification
NCT01975142
Legal entity responsible for the study
Institut Curie
Funding
Roche
Disclosure
All authors have declared no conflicts of interest.