Efficacy, safety and circulating tumor cell dynamics in patients treated with Eribulin for HER2-negative advanced breast cancer - results from the phase II DETECT IVb trial.

Eribulin is a non-taxane microtubule inhibitor that showed survival benefits for pretreated metastatic breast cancer (MBC) patients. Circulating tumor cells (CTCs) are a prognostic marker, but their role in predicting response to specific MBC treatments is less clear. In this trial, we assessed the clinical outcome and its association with CTC-dynamics in HER2-negative MBC treated with eribulin. HER2-negative MBC-patients were screened for CTCs within the DETECT study program using the CellSearch® technology (Menarini Silicon Biosystems; Bologna, Italy). Patients with HER2-negative CTCs were eligible for the single-arm DETECT-IVb study treatment with eribulin. Primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS), CTC-clearance rate and safety. Median PFS and OS were 4.6 months and 13.4 months, respectively. Multivariable adjusted analyses showed that patients with CTC-clearance at first follow-up (34.7%) had significantly improved PFS (p = 0.043) but not OS (p = 0.192) compared to patients with at least 1 CTC. Likewise, patients with CTC-clearance at the end of the treatment (23.1%) achieved a significantly better PFS (p = 0.015) but not OS (p = 0.218). Neutropenia, leukopenia, anemia and fatigue were the most common adverse events and no new or unexpected safety signals were obtained. In this trial, we could confirm eribulin as an effective treatment option in high-risk HER2-negative MBC. CTCs proved their role as a prognostic marker and our results support the potential role of CTC dynamics as an early biomarker of treatment response to eribulin. EudraCTNo2013-001269-18 http://ClinicalTrials.gov , TRN NCT02035813, Registration date 2014-01-12.