Effects of dose modification of eribulin mesylate in patients with locally recurrent or metastatic breast cancer.
157 Background: Eribulin mesylate is indicated for patients with metastatic breast cancer after treatment with ≥ 2 prior chemotherapeutic regimens. Recommended dosing is 1.4 mg/m2on specific cycle days with options for dose modification (dose reduction/delay) based on severity and duration of specific toxicities. The goal for therapy is to administer the full studied dose; however, for patients experiencing an adverse event (AE) the impact of dose modification has not yet been explored. The purpose of this study was to determine the effects of dose modification due to AEs on duration of therapy. Methods: Data from patients receiving eribulin in a phase III open label, randomized clinical trial evaluating eribulin vs. ‘Treatment of Physician’s Choice’ (E7389-G000-305) was utilized. Analyses were performed on the population with AEs. Patients were classified into a dose modification cohort for any dose reduction/delay related to an AE, or a dose non-modification cohort for patients who did not receive a dose modification but experienced an AE. Descriptive statistics were calculated and survival analyses were conducted. Results: Overall, 462 patients had an AE that was treatment-related: 204 patients (44.2%) had dose modification (delay only [61.8%], reduction only [17.6%], and both [20.6%]), and 258 (55.8%) did not have dose modification. Average age was 55 years, and most patients were Caucasian (92.4%). Patients with dose modification had a mean of 7.36 (±4.56) chemotherapy cycles and a median of 143 treatment days, while patients without modification had a mean of 5.71 (±3.68) cycles and a median of 105 treatment days (p < 0.001). The median PFS was also longer in the dose modification cohort (130 vs. 92 days based on independent review). However, there were no statistically significant correlation between PFS and dose modification after adjusting for the length of treatment exposure using time-dependent and landmark approaches. Conclusions: Delaying or reducing the dose of eribulin in patients who experience AEs may allow patients to remain on therapy longer. Further prospective studies are warranted to confirm the impact on overall efficacy and safety.