Effects of neratinib (N) on health-related quality of life (HRQoL) in early-stage HER2+ breast cancer (BC): longitudinal analyses from the phase III ExteNET trial

Abstract

Background: The international, randomized, placebo (P)-controlled phase III ExteNET trial (NCT00878709) showed that N for 1 y after trastuzumab-based adjuvant therapy significantly improved 2-y invasive disease-free survival in early HER2+BC patients (pts) (HR 0.67; 95% CI 0.50-0.91; p=0.0091) [Chan et al. Lancet Oncol 2016]. Detailed longitudinal evaluation of HRQoL was an exploratory endpoint of ExteNET. Methods: 2840 pts received N 240 mg/d or P for 1 yr. Pts completed FACT-B and EQ- 5D questionnaires at baseline and months (M) 1, 3, 6, 9, and 12. Changes in scores from baseline were compared between groups using ANCOVA with no imputation for missing values. Sensitivity analyses using alternative methods were applied. Changes in HRQoL scores were considered to be clinically meaningful if greater than minimal clinically important differences (MCID) reported in the literature. Results: 2407 pts were evaluable for FACT-B (N, n=1171; P, n=1236), and 2427 for EQ-5D (N, n=1186; P, n=1241). Compliance with questionnaires exceeded 85%. N was associated with decreased HRQoL scores at M1 vs P, after which between-group differences diminished (Table). They were consistently less than MCIDs, except for physical well-being (PWB) subscale at M1. BC subscale (BCS) showed small improvements with N at M3-M9, all less than MCIDs. Different sensitivity methods did not alter the results. Conclusions: N was associated with decreased HRQoL, in particular in PWB, at M1, possibly due to N-related diarrhea. Based on their small magnitude, differences observed after M1 in PWB favoring P and in BCS favoring N, may not be clinically important. (Table Presented).