Abstract P6-11-14: Post-hoc safety and tolerability assessment in patients receiving palliative radiation during treatment with eribulin mesylate for metastatic breast cancer
Authors: Yardley DA , Vahdat L , Rege J , Cortés J , Wanders J , Twelves C 
Published: August 2014

Abstract
Background: Management of advanced breast cancer frequently includes palliative radiation therapy (RT) and many chemotherapy agents are radiation-sensitizers. We assessed whether the safety profile of eribulin differed between metastatic breast cancer (MBC) patients receiving eribulin alone and those who also received palliative RT.
Methods: Two previous phase 2 and 3 eribulin trials (Studies 211 and 305, respectively) enrolled a total of 794 patients with locally recurrent or MBC who had received 2–5 prior chemotherapy regimens. In both trials eribulin mesylate (1.4 mg/m2) was given on Days 1 and 8 of a 21-day cycle and intercurrent palliative RT was permitted. In this post-hoc analysis, patient-level data were pooled for a descriptive comparison of adverse events (AEs) between the patients who received RT during their study treatment and those who did not. RT delivered within 3 weeks of initiation of eribulin or RT encompassing &gt;30% of marrow was excluded. If palliative RT was utilized on study, the protocol requirements were as follows: indications included bone pain, bronchial obstruction, ulcerating skin lesions; the total field for palliative RT was not to involve &gt;10% of total bone marrow; and the irradiated lesion was not to be used for tumor response assessment. During palliative RT, eribulin treatment was to be delayed and then resumed when the patient had recovered from any RT-associated toxicities.
Results: Of the 794 patients (291 patients in Study 211 and 503 in Study 305) who received eribulin, 44 (5.5%) received palliative RT.

The majority (26/44, 60%) received ≥10 cGys. Baseline demographics were similar between the RT (n = 44) and no RT (n = 750) subgroups, as was the use of concomitant medications. Six of 44 patients (14%) continued eribulin treatment during the palliative RT, contrary to protocol recommendation. The AE profiles over the course of the study were similar between subgroups. The most common events reported in both subgroups (RT vs no RT) were neutropenia (50% vs 55%), alopecia (48% vs 51%), nausea (43% vs 40%), fatigue (39% vs 32%), and asthenia (27% vs 32%). There were no significant differences in Grade 3/4 treatment-emergent AEs, or other AEs (total AEs: 56.8% vs 58.9%). Potential localized events that were more frequent in the RT subgroup were bone pain (27% vs 15%), back pain (27% vs 10%), and musculoskeletal pain (14% vs 8%); many represent potential indications for RT. Half (22/44) of patients started RT 30 days after the start of eribulin treatment. Palliative RT was short in duration; 33 (75%) patients received ≤7 days, and 11 (25%) patients received 8–20 days. Six of the 44 irradiated patients (14%) had a skin-related toxicity, but most were alopecia (7/8 events) and all were associated with eribulin.
Conclusions: This post-hoc subgroup analysis suggests palliative RT while receiving eribulin treatment does not appear to have an effect on the AE profile of eribulin. Further studies to define the optimal use of radiotherapy with eribulin are warranted.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-11-14.