Clinical utility of circulating tumour cell-based monitoring of late-line chemotherapy for metastatic breast cancer: the randomised CirCe01 trial

Luc Cabel, Frédérique Berger, Paul Cottu, Delphine Loirat, Aurore Rampanou, Etienne Brain, Stacy Cyrille, Hugues Bourgeois, Nicolas Kiavue, Elise Deluche, Sylvain Ladoire, Mario Campone, Jean-Yves Pierga, Francois-Clement Bidard, Luc Cabel, Frédérique Berger, Paul Cottu, Delphine Loirat, Aurore Rampanou, Etienne Brain, Stacy Cyrille, Hugues Bourgeois, Nicolas Kiavue, Elise Deluche, Sylvain Ladoire, Mario Campone, Jean-Yves Pierga, Francois-Clement Bidard

Abstract

Background: CirCe01 trial aimed to assess the clinical utility of circulating tumour cell (CTC)-based monitoring in metastatic breast cancer (MBC) patients beyond the third line of chemotherapy (LC).

Methods: CirCe01 was a prospective, multicentre, randomised trial (NCT01349842) that included patients with MBC after two systemic LC. Patients with ≥5 CTC/7.5 mL (CellSearch®) were randomised between the CTC-driven and the standard arm. In the CTC arm, changes in CTC count were assessed at the first cycle of each LC; patients in whom CTC levels predicted early tumour progression had to switch to a subsequent LC.

Results: Greater than or equal to 5 CTC/7.5 mL were observed in N = 101/204 patients. In the CTC arm (N = 51), 43 (83%) and 18 (44%) patients completed CTC monitoring in the third and fourth lines, respectively, and 18 (42%) and 11 (61%) of these patients, respectively, had no CTC response. Thirteen (72%) and 5 (46%) of these patients underwent early switch to the next LC. Overall survival was not different between the two arms (hazard ratio = 0.95, 95% confidence interval = [0.6;1.4], p = 0.8). In subgroup analyses, patients with no CTC response who switched chemotherapy experienced longer survival than patients who did not.

Conclusions: Due to the limited accrual and compliance, this trial failed to demonstrate the clinical utility of CTC monitoring.

Clinical trial registration: NCT, NCT01349842, https://ichgcp.net/clinical-trials-registry/NCT01349842 , registered 9 May 2011.

Conflict of interest statement

F.-C.B. and J.-Y.P. report grants and non-financial support from Menarini Silicon Biosystem, during the conduct of the study. M.C. reports personal fees and other from Novartis, during the conduct of the study; other from Sanofi, Servier, Abbvie, Accord and Astra Zeneca; personal fees from Lilly, outside the submitted work. The other authors have no disclosures.

Figures

Fig. 1. Design of the CirCe01 trial.
Fig. 1. Design of the CirCe01 trial.
CTC circulating tumour cells, L line of systemic chemotherapy, PS performance status.
Fig. 2. Study flow chart.
Fig. 2. Study flow chart.
CTC: circulating tumor cells.
Fig. 3. Survival.
Fig. 3. Survival.
Progression-free survival (a) and overall survival (b) according to the study arm. Arm A CTC-based monitoring, Arm B standard monitoring.
Fig. 4. CTC level variation and protocol…
Fig. 4. CTC level variation and protocol compliance at the third and fourth lines of chemotherapy.
CTC circulating tumour cell, CT chemotherapy.

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