Background: Eribulin mesylate (EM) is a microtubule inhibitor shown to improve survival in patients with metastatic breast cancer (MBC) who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. A common grade 3/4 toxicity of EM is neutropenia which may result in dose adjustments and dose delays. To minimze neutropenic complications, granulocyte colony-stimulating factor (GCSF or GMCSF) may be utilized, as well as dose modifications or treatment discontinuation. The purpose of this analysis is to examine the impact of treatment modifications and/or GCSF administration in patients experiencing EM mediated neutropenia on treatment duration.
Methods: A retrospective, cross-sectional claims database analysis was conducted in the MedAssets health system database on EM treated MBC patients experiencing neutropenia in the inpatient or outpatient setting between December 2010 and September 2012. EM dosing and dosing changes identified 110 EM treated MBC patients using hospital charge records which consist of drug description, quantity administered, and frequency of administration. Treatment patterns were discerned using service dates for each charge record. Adverse events, including neutropenia, were identified using diagnosis codes and/or presence of charge codes for common treatments during the EM treatment period. Patients were classified into those administered GCSF anytime during EM treatment (N = 24) and those who were not (N = 86). A negative binomial generalized linear regression model was used to estimate the effect of GCSF use and dose modification on the total number of EM treatments during a patient’s course of treatment. The model was adjusted for common treatment side effects (anemia, fatigue, nausea, constipation, diarrhea, peripheral neuropathy and alopecia), cancer type (ER+ and HER+) and above 65 years of age. Due to limitations in administrative data certain molecular subtypes, line of therapy, and grade and duration of neutropenia could not be identified.
Results: Approximately 22% of EM MBC patients with neutropenia were treated with GCSF. Among patients with EM related neutropenia 38.1% experienced either a dose adjustment (23.7%) or treatment delay (26.8%) with 81.4% of these modifications occurring in the first three cycles. After controlling for age, molecular subtype, and side effects—EM treated MBC patients also receiving concomitant GCSF administered during EM treatment were estimated to have a higher number of EM infusions (1.5 infusions, p<0.05) as compared to those EM treated MBC pts who were not administered GCSF. In addition, patients experiencing treatment modifications were estimated to have more EM infusions (1.8 infusions, p<0.0001) than those without modifications.
Conclusion: EM treatment related neutropenia managed with GCSF and/or dose modification facilitated the ability to continue EM administrations in MBC patients.
