Abstract P3-13-04: Effect of age on tolerability and efficacy of eribulin and capecitabine in patients with metastatic breast cancer treated in study 301
Authors: Kaufman PA , Yelle L , Cortes J , Perez EA , Awada A , Wanders J , Olivo MS , He Y , Dutcus CE , Twelves C 
Published: August 2014

Abstract
Background:
The Phase III trial (NCT00337103) compared eribulin (E) with capecitabine (C) in patients (pts) with metastatic breast cancer (MBC) in the 1st-, 2nd-, and 3rd-line setting. Median overall survival (OS) was 15.9 and 14.5 months (HR 0.88; 95% CI 0.77, 1.00; P = 0.056) and median progression-free survival (PFS) was 4.1 and 4.2 months (HR 1.08; 95% CI 0.93, 1.25; P = 0.30) for E and C, respectively. This analysis compares toxicity and efficacy of E and C in relation to age.
Material and methods:
In this post-hoc exploratory analysis, the effect of age on the incidence of adverse events (AEs), OS, PFS, and objective response rate (ORR) with E and C were analyzed for two age groups: ≤65 years (E, n = 468; C, n = 491) and &gt;65 years (E, n = 86; C, n = 57). For OS and PFS, analyses were stratified by HER2 and geographic region.
Results:
With increasing age, the proportion of pts with worse performance status (PS ≥1: 54.5% vs 69.2% for ≤65 and &gt;65 years, respectively), ER+ (47.4% vs 57.3%), and PgR+ MBC (41.3% vs 45.5%) increased, and the proportion with triple-negative MBC decreased (26.6% vs 20.3%). With both treatments, AEs were reported in a higher proportion of pts in the older age group, this becoming more apparent for grade 3+ AEs (E: 64.6% vs 70.2%, and C: 45.0% vs 54.4% for ≤65 and &gt;65 respectively). With E, there was a trend for increased incidence of grade 3/4 neutropenia (45.0% vs 50.0%) and leukopenia (13.7% vs 22.6%) but, in contrast, decreased peripheral sensory neuropathy (3.9% vs 1.2%) with increasing age. For C, there was a trend for increased palmar-plantar erythrodysethesia syndrome (total: 44.4% vs 50.9%; grade 3/4: 14.1% vs 17.5%), and grade 3/4 fatigue (1.8% vs 7.0%) and diarrhea (4.7% vs 10.5%) with increasing age; emesis and nausea were similar for both age groups. Dose adjustments due to AEs with E were slightly higher in the older age group: withdrawals 7.4% vs 10.7%; dose reductions 31.1% vs 36.9%; and dose delays 30.9% vs 36.9%. With C, there was a trend for an increased incidence of withdrawals (9.2% vs 21.1%) and dose delays (34.2% vs 49.1%) due to AEs with increasing age: the incidence of dose reductions was slightly higher in the older age group (31.3% vs 36.8%). In an unadjusted analysis, a trend for improved OS with E vs C was observed in both subgroups (≤65 years: median 15.8 vs 14.5 months; HR 0.90; 95% CI 0.78, 1.04; P = 0.16, and &gt;65 years: median 18.4 vs 14.1 months; HR 0.74; 95% CI 0.50, 1.12; P = 0.16). PFS and ORR for E and C were: median PFS: E, 4.0 and 5.4 months; C, 4.2 and 5.9 months; ORR: E, 10.9% and 11.6%; C, 11.6% and 10.5%, in the ≤65 and &gt;65 groups respectively.
Conclusions:
This exploratory and unadjusted analysis suggests a trend for improved OS with E in both younger and older pts with MBC. With both treatments there was a suggestion that AEs were reported in a higher proportion of pts in the older age group, this becoming more apparent for grade 3+ events. Specifically, these data suggest an increased incidence of grade 3/4 diarrhea, dose delays, and study withdrawal due to AEs in pts treated with C, and potentially suggest that with E there may be less difference between the AE profile in younger vs older pts than with C.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-13-04.