Abstract P2-02-17: T-DM1 in HER2-negative metastatic breast cancer patients with HER2-amplified circulating tumor cells: Current status of the CirCe T-DM1 phase II trial

Abstract

Abstract Background: Liquid biopsy can reassess key therapeutic targets in metastatic breast cancer. Several studies showed that a low albeit significant rate of metastatic breast cancer initially considered as HER2-negative can be reclassified as HER2-positive by systematic biopsy procedures. We report here the current status of the CirCe T-DM1 trial [NCT01975142] which aims to demonstrate the clinical utility of HER2 status reassessment on circulating tumor cells (CTCs). Methods: The first step of the trial consists in CTC count and HER2/CEP17 FISH on detected CTCs (CellSearch, Janssen Diagnostics) in patients (pts) with measurable disease progressing after the second line of chemotherapy. Pts with amplified CTCs (HER2/CEP17 ratio equal or higher than 2.2) are eligible to the treatment step of the study in two distinct cohorts: low CTC count (1 or 2 HER2-amplified CTCs) and high CTC count (3 and more HER2-amplified CTCs). In the treatment step has a Simon's two stage design, the anti-HER2 antibody-drug conjugate T-DM1 being administered until tumor progression. The primary objective of the trial is the confirmed response rate (RECIST). This trial is supported by Roche. Results: CirCe T-DM1 has been initiated in 10 centers in France. As of June 2015, 105 metastatic breast cancers pts considered as HER2-negative were screened. 29 pts (27%) had no CTC detected, 68 pts (65%) had at least 1 CTC detected with no HER2 amplification, and 8 pts (8%) exhibited HER2-amplified CTCs. Among the 8 pts, 1 pt had 5 HER2-amplified CTC, 2 pts had 2 HER2-amplified CTC and 5 pts had 1 HER2-amplified CTC. HER2/CEP17 ratios among HER2-amplified CTCs ranged from 2.5 to 7. Five of the 8 pts were treated by T-DM1. One objective confirmed partial tumor response has been observed (20%). Conclusion: The accrual is ongoing; the first efficacy assessment will occur after having treated 14 pts. This innovative trial highlights the promise and the complexity of liquid biopsy-based programs in the era of precision medicine: scarcity of the target, reliability and reproducibility of the target assessment, major efficacy when the target is matched to the appropriate drug. Citation Format: Bidard F-C, Romieu G, Jacot W, Cottu P, Dieras V, Lerebours F, Servent V, Luporsi E, Lortholary A, Tubiana-Mathieu N, Espie M, Bollet M, Bourgeois H, Renaud N, Pelissier S, Armanet S, Baeten K, Pierga J-Y. T-DM1 in HER2-negative metastatic breast cancer patients with HER2-amplified circulating tumor cells: Current status of the CirCe T-DM1 phase II trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-02-17.