A Phase 1 Dose Escalation Study of Eribulin in Combination with Weekly Carboplatin for the Treatment of Metastatic Breast Cancer

Abstract

Background: Metastatic breast cancer is a common and devastating diagnosis. New strategies for treatment are needed to help improve outcomes. Eribulin is an anti-microtubule agent approved in 2010 for advanced breast cancer. Combination with other chemotherapeutic agents provides an alternative treatment option for these patients. Purpose: This study evaluates the safety, tolerability and activity of eribulin and weekly carboplatin in a dose-escalation schema in patients with metastatic breast cancer. Methods: Patients were treated with eribulin and carboplatin AUC 2 administered on the first and eighth days of a 21-day cycle. Three doses of eribulin (0.9, 1.1 and 1.4 mg/m2 ) were examined. An additional 10 patients were enrolled into an expansion cohort at the recommended Phase 2 dose. Results: A total of 19 patients were treated, including 10 patients in the dose expansion cohort. There was no dose limiting toxicity related to the study therapy in the dose escalation cohorts. Grade 3 toxicities included neutropenia (21%), anemia (10%), fatigue (10%), peripheral sensory neuropathy (10%), infusion related reactions (5%), pericardial effusion (5%), diarrhea (5%) and pleural effusion (5%). Twenty-six percent of patients had grade 4 neutropenia, but there were no events of sepsis or febrile neutropenia. The maximum tolerated dose (MTD) of eribulin in combination with carboplatin AUC 2 was determined to be 1.4 mg/m2 . Four patients experienced clinical benefit, 2 patients with stable disease greater than 6 months and 2 patients with partial response, demonstrating a clinical benefit rate of 21%. Conclusion: Eribulin and weekly carboplatin appeared to be safe and well tolerated with demonstrated clinical benefit. The recommended Phase 2 dose level was 1.4 mg/m2 of eribulin. Further studies can be pursued for this combination regimen to establish its efficacy.