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.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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. TRIAL REGISTRATION: EudraCTNo2013-001269-18 http://ClinicalTrials.gov , TRN NCT02035813, Registration date 2014-01-12.