Impact of Treatment Modification on Treatment Duration in Metastatic Breast Cancer Patients Treated with Eribulin Mesylate
Introduction: EM is a microtubule inhibitor shown to improve overall survival in metastatic breast cancer patients who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. There are side effects of EM, including neutropenia, anemia, asthenia/fatigue, alopecia, peripheral neuropathy, nausea, and constipation. While some physicians discontinue treatment due to side effects, others manage side effects using dose delays/skipped doses and/or dose modifications. The purpose of this retrospective study is to analyze the impact of EM treatment modifications (dose modification) on therapy duration.
Description: This study examined dosing and treatment patterns during EM treatment. The study population included MBC pts in the MedAssets health system database treated with EM in the hospital inpatient or outpatient setting from December 2010 to September 2012. Treated pts, dosing and dosing changes were identified administratively using hospital charge records which include drug description, quantity given and frequency of administration. Treatment patterns were discerned using service dates for each charge record. Adverse events were identified using diagnosis codes and/or the presence of charge codes for common treatments during the EM treatment period. Between group differences were tested using ANOVA for continuous variables and Chi-Square for categorical variables. A negative binomial generalized linear regression model was used to estimate the effect of dose modification on the number of EM treatments. The model was adjusted for common treatment side effects (neutropenia, anemia, fatigue, nausea, constipation, diarrhea, peripheral neuropathy and alopecia), cancer type (ER+ and HER+) and age >65 years. Due to limitations of administrative data HER2- and triple negative cancer pts could not be identified; therefore their effects on treatment could not be measured.
Summary: Of 510 pts in the cohort 34.1% had either a dose decrease (23.3%) or treatment delay/missed (20.2%) during EM treatment. Approximately 30% of pts with a dose decrease subsequently increased their dose. More than 80% of the treatment modifications occurred in the first (21.3%), second (48.3%) or third (11.5%) cycle. The most common side effects (>15%) in this population were nausea (60.0%), neutropenia (41.0%), anemia (25.1%) and fatigue (15.1%). Pts with neutropenia (40.7% vs 29.6%, p<.001), fatigue (46.8% vs 31.9%, p<.05), nausea (39.2% vs 26.5%, p<.001) and constipation (47.9% vs 32.7%, p<.05) were more likely to have a dose modification as were hormone positive pts (58.6% vs 48.5%, p<.05). No difference was seen in HER2 positive pts (19.0% vs 17.0%, p = 0.57) or in age ≥65 (28.7% vs 26.2%, p = 0.540) between the two cohorts. After adjusting for other factors, pts with a dose modification were estimated to have more treatments (1.90, p<.0001) compared to those who did not.
Conclusion: Patients who had a dose modification, a common strategy to handle adverse events, were able to stay on therapy longer.
Reference: Cortes J, Montero AJ, Glück S. Eribulin mesylate, a novel microtubule inhibitor in the treatment of breast cancer. Cancer Treatment Reviews. 2012;38(2):143-151.