Abstract P5-17-03: Quality of life results from a phase 2, multicenter, single-arm study of eribulin mesylate plus trastuzumab as first-line therapy for locally recurrent or metastatic HER2+ breast cancer
Authors: Schwartzberg Lee , Wilks Sharon , Puhalla Shannon , O'Shaughnessy Joyce , Berrak Erhan , Song James , Cox David , Vahdat Linda 
Published: May 2015

Abstract
Introduction: Eribulin mesylate is a nontaxane microtubule dynamics inhibitor that has showed an overall survival benefit relative to other commonly used agents in patients with ≥2 prior MBC therapies. Primary data from a phase 2 trial for first-line eribulin + trastuzumab [TRAS] in HER2+ patients with MBC showed an objective response rate of 71%, clinical benefit rate of 84.6%, disease control rate of 96.2%, PFS of 11.6 months, and tolerability similar to known profiles for these agents. Here, we present prespecified QoL, efficacy, and safety/tolerability results.
Methods: Patients received eribulin mesylate 1.4 mg/m2 IV on days 1 and 8 of each 21-day cycle and initial TRAS (8 mg/kg IV/day 1), followed by 6 mg/kg on day 1 of each subsequent cycle. Response, PFS, QoL as measured by EORTC QoL assessment tool (QLQ-C30) and QLQ-BR23, and tolerability were assessed. Percentage of patients with at least ±10-point change from baseline was calculated at each visit. Time to deterioration was defined as time from first dose to worsening in QoL score that reached minimally clinically important difference (MID) (ie, 10 points in global health status [GHS] in QLQ-C30) without further improvement of at least MID; this was estimated overall and by response status.
Results: At cycle 6 (n=44; completion rate=84.6% of 52 patients enrolled), more patients fell in the stable category (within +/-10 points change from baseline), except for pain (47.7% with improvement), cognitive functioning (45.5% worsening), fatigue and systemic therapy side effects (50% worsening for each), and arm symptoms (47.7% improvement) (Table). Median times to deterioration for GHS/QoL were 7.6 months overall (n=51), and 7.6 and 7.0 months for responders (n=36) and nonresponders (n=15), respectively (HR 0.73; 95% CI 0.32, 1.68; P=0.446). Mean symptom scores in EORTC QLQ-C30 were significantly correlated with corresponding AE rates for fatigue (r=0.31), nausea/vomiting (r=0.50), pain (r=0.41), dyspnea (r=0.49), insomnia (r=0.35), constipation (r=0.30), and diarrhea (0.40; P≤0.03 for all comparisons). The most common treatment-related AEs (all grade incidence ≥25%) were alopecia (88.5%), fatigue (69.2%), peripheral neuropathy (69.2%), neutropenia (59.6%), nausea (46.2%), diarrhea (32.7%), anemia (25%), constipation (25%), and decreased appetite (25%).
Table. Qol EORTC QLQ-C30 Scores: Change from Baseline to Cycle 6 (n=44)Functional orCategory, n (%)Symptom ScaleImprovedStableWorsenedGHS/Qol13 (29.5)23 (52.3)8 (18.2)Physical10 (22.7)26 (59.1)8 (18.2)Role13 (29.5)20 (45.5)11 (25.0)Emotional17 (38.6)18 (40.9)9 (20.5)Cognitive6 (13.6)18 (40.9020 (45.5)Social12 (27.3)18 (40.9)14 (31.8)Fatigue14 (31.8)8 (18.2)22 (50.0)Nausea/vomiting9 (20.5)24 (54.5)11 (25.0)Pain21 (47.7)14 (31.8)9 (20.5)Dyspnea12 (27.3)19 (43.2)13 (29.5)
Conclusions: Given the improvements in pain and in arm and breast symptoms, long median time to deterioration in functioning/symptom scales in this analysis, and the tumor response rates and safety profile in the primary analysis, combination eribulin/TRAS may be an acceptable treatment option for locally recurrent or HER2+ MBC and merits further study in larger clinical trials.
Citation Format: Lee Schwartzberg, Sharon Wilks, Shannon Puhalla, Joyce O'Shaughnessy, Erhan Berrak, James Song, David Cox, Linda Vahdat. Quality of life results from a phase 2, multicenter, single-arm study of eribulin mesylate plus trastuzumab as first-line therapy for locally recurrent or metastatic HER2+ breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-17-03.