Abstract P5-15-08: A phase 2 study of eribulin as early-line treatment for HER2- MBC: Evaluation of efficacy, toxicity, and patient-reported outcomes
Authors: Metzger O , Lin NU , Schneider B , Faggen M , Come S , Openshaw T , Constantine M , Walsh J , Giobbie-Hurder A , Burstein HJ , Mayer EL 
Published: May 2019

Abstract
Background:
Patient-reported outcomes (PROs) independently and directly describe patient (pt) treatment experiences, complement clinician reports, and are increasingly included in drug development. Eribulin (E) has activity in metastatic breast cancer (MBC) previously treated with &gt; 2 regimens. Limited data are available on the activity of E in earlier lines. This phase II single arm study evaluated the activity, safety, and PROs of E in an earlier line setting for HER2- MBC.
Methods: Eligible pts had HER2- MBC, 0-1 prior lines of chemotherapy, and enrolled into one of two parallel cohorts: HR+, TNBC. E was dosed 1.4 mg/m2 weekly, 2 wk on/1 wk off; 1 cycle = 3 wks. The primary objective was overall response rate (ORR); additional objectives included progression-free survival (PFS) and safety. Correlative PRO endpoints included description and comparison of toxicity evaluation by PROs vs provider-report for degree of concordance or divergence for each class of toxicity, and description of QOL over time. Neuropathy was evaluated by the FACT-Neurotoxicity subscale, as well as exploration of predictive host polymorphisms. PRO instruments (PRO-CTCAE, FACT-B and FACT-NTX) were administered electronically at baseline, cycles 1-3, then every other cycle.
Results: 83 pts enrolled: 45 HR+ and 38 TNBC. Median age was 56 (range: 34-87). 55.4% were first line, and 66% had received previous taxane in the adjuvant or metastatic setting. ORR for all pts was 25.3% (90% CI: 18%-34%); 35.6% in HR+ (90% CI: 24%-49%) and 13.2% in TNBC (90% CI: 5%-26%). mPFS estimate was 5.8 months (mo) for all pts, HR+ 6.2 mo (90% CI: 5.9-8.7) and TNBC 4.0 mo (90% CI: 3.5-4.8). Related toxicities occurring in &gt; 20% of pts were: fatigue (61.4% overall, 32.5% G1, 27.7% G2, 1.2% G3), alopecia (51.8% overall, 16.9% G1, 32.5% G2), nausea (39.8% overall; 26.5% G1, 12.0% G2, 1.2% G3), peripheral sensory neuropathy (36.1% overall; 18.1% G1, 13.3% G2, 4.8% G3), decreased neutrophil count (32.5% overall; 3.6% G1; 4.8% G2, 13.3% G3, 10.8% G4), peripheral motor neuropathy (22.9% overall, 13.3% G1, 6.0% G2, 3.6% G3), and mucositis (20.5% overall, 16.9% G1, 2.4% G2, 1.2% G3). FACT-B Breast Cancer Concern (BCC) and Trial Outcome Index (TOI) scores were stable during therapy. The greatest mean improvement in summed BCC (mean change 3.3) and TOI (mean change 7.9) compared to baseline occurred at cycle 9 in pts with stable disease. Changes from baseline in the NTX and TOI of FACT-NTX worsened during the first 7 cycles of therapy (mean changes NTX 5.3, TOI 4.8). Pharmacogenomic analysis exploring host polymorphisms and development of neuropathy is ongoing.
Conclusions: PROs are indispensable in the evaluation of anti-cancer agents in clinical trials. In this phase II trial, E demonstrated activity and safety in early lines of therapy for HER2- MBC. Additionally, improved QOL metrics were observed among pts experiencing stable disease. CTCAE rates of severe neuropathy were low, however PRO testing by FACT-NTX highlights progressive worsening of neurotoxicity. In contrast to classic CTCAE criteria producing aggregate estimates of toxicity, this phase II trial shows longitudinal collection of PROs provides meaningful, complementary, and dynamic clinical information.
Citation Format: Metzger O, Lin NU, Schneider B, Faggen M, Come S, Openshaw T, Constantine M, Walsh J, Giobbie-Hurder A, Burstein HJ, Mayer EL. A phase 2 study of eribulin as early-line treatment for HER2- MBC: Evaluation of efficacy, toxicity, and patient-reported outcomes [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-15-08.