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.
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.
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.Table:
|Adjusted† mean difference in change from baseline:|
|Scale||MCID range||N vs P|
|EQ health state||7–10||–2.7*||0.1||–1.3*||–0.7||–0.4|
For baseline score;*
Statistically significant at p
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.
Clinical trial identification
Legal entity responsible for the study
Wyeth, Pfizer and Puma Biotechnology
S. Delaloge: Grants and personal fees from Roche and GSK. Y. Ye: Employment: Puma Biotechnology Inc. M. Buyse: Employee and shareholder of IDDI. A. Chan: Personal fees for educational meetings from Pfizer, Amgen. Non-financial support from Puma Biotechnology outside the submitted work. C. Barrios: Grants from Amgen, AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, Roche, Celgene, Sanofi, Lilly, Puma. Personal fees from GSK, Novartis, Pfizer, Roche, Eisai. B. Ejlertsen: Grants to institution from NanoString, Novartis, and Roche, outside the submitted work. Travel support for educational meetings from AstraZeneca and Celgene. G. von Minckwitz: Research funding to the institution from Amgen, Roche, Novartis, Celgene, Teva, AstraZeneca, Myriad Genetics, AbbVie and Vifor Pharma. M. Gnant: Grants from Sanofi-Aventis, Novartis, Roche, GSK, Pfizer, Smith Medical. Personal fees from Novartis, AstraZeneca, Accelsiors, Eisai. S. Moran, A.H. Auerbach: Employment and stock options: Puma Biotechnology Inc. All other authors have declared no conflicts of interest.