TY - JOUR
T1 - Patterns of occurrence and implications of neratinib-associated diarrhea in patients with HER2-positive breast cancer
T2 - Analyses from the randomized phase III ExteNET trial
AU - Mortimer, Joanne
AU - Di Palma, Jack
AU - Schmid, Kendra
AU - Ye, Yining
AU - Jahanzeb, Mohammad
N1 - Funding Information:
This study was funded by Wyeth, Pfizer, and Puma Biotechnology Inc. Puma Biotechnology Inc. also funded the provision of editorial support.
Funding Information:
JM has performed a consulting or advisory role for Puma Biotechnology (ExteNET Data and Safety Monitoring Board). JdP has stock or other ownership in Novobiotics and Creatics, has received honoraria from Braintree Laboratories and Takeda, performed a consulting or advisory role for Braintree Laboratories and speakers’ bureaus for Takeda and AstraZeneca, and is a member of the ExteNET Data and Safety Monitoring Board. KS has performed a consulting or advisory role for Puma Biotechnology (ExteNET Data and Safety Monitoring Board). YY is a former employee of Puma Biotechnology and owns stock in Puma Biotechnology and Amgen. MJ has received honoraria from Foundation Medicine; performed consulting or advisory roles for Novartis; Genentech, Lilly, Bristol-Myers Squibb, and Pfizer; received research funding from Genentech, Ariad, Clovis Oncology, and Abb-Vie, travel and accommodation expenses from Novartis, Genentech, Lilly, Ariad, Pfizer, and Bristol-Myers Squibb; and is a member of the ExteNET Data and Safety Monitoring Board for Puma Biotechnology.
PY - 2019/2/27
Y1 - 2019/2/27
N2 - Background: We characterized patterns of occurrence and the impact of neratinib-associated diarrhea in the absence of protocol-directed antidiarrheal prophylaxis or a formal diarrhea management plan using data from Extended Adjuvant Treatment of Breast Cancer with Neratinib (ExteNET). Methods: ExteNET is a multicenter, double-blind, placebo-controlled, randomized phase III trial involving community-based and academic institutions in 40 countries. Women with HER2-positive early-stage breast cancer with prior standard primary therapy and trastuzumab-based (neo)adjuvant therapy were randomized to neratinib 240 mg/day or placebo for 12 months. Safety, a secondary outcome, was assessed using the National Cancer Institute Common Terminology Criteria version 3.0. Health-related quality of life by diarrhea grade was assessed using Functional Assessment of Cancer Therapy-Breast (FACT-B). Results: Two thousand eight hundred sixteen women (1408 per group) were safety-evaluable. Grade 3 and 4 diarrhea occurred in 561 (39.8%) and 1 (0.1%) patients with neratinib versus 23 (1.6%) and 0 patients with placebo, respectively. In the neratinib group, 28.6% of patients had grade 3 events during month 1 decreasing to ≤ 6% after month 3. The median cumulative duration of grade 3/4 diarrhea with neratinib was 5 days (interquartile range, 2-9). Serious diarrheal events (n = 22, 1.6%) and diarrheal events requiring hospitalization (n = 20, 1.4%) were rare with neratinib. Changes in FACT-B total score by diarrhea grade in the neratinib group did not meet the threshold for clinically important differences. Conclusions: In the absence of antidiarrheal prophylaxis, neratinib-related diarrhea is short-lived and not associated with complications or long-term sequelae. This suggests that targeted preventive management with antidiarrheal prophylaxis early during neratinib treatment is appropriate. Trial registration: ClinicalTrials.gov NCT00878709. Registered 9 April 2009.
AB - Background: We characterized patterns of occurrence and the impact of neratinib-associated diarrhea in the absence of protocol-directed antidiarrheal prophylaxis or a formal diarrhea management plan using data from Extended Adjuvant Treatment of Breast Cancer with Neratinib (ExteNET). Methods: ExteNET is a multicenter, double-blind, placebo-controlled, randomized phase III trial involving community-based and academic institutions in 40 countries. Women with HER2-positive early-stage breast cancer with prior standard primary therapy and trastuzumab-based (neo)adjuvant therapy were randomized to neratinib 240 mg/day or placebo for 12 months. Safety, a secondary outcome, was assessed using the National Cancer Institute Common Terminology Criteria version 3.0. Health-related quality of life by diarrhea grade was assessed using Functional Assessment of Cancer Therapy-Breast (FACT-B). Results: Two thousand eight hundred sixteen women (1408 per group) were safety-evaluable. Grade 3 and 4 diarrhea occurred in 561 (39.8%) and 1 (0.1%) patients with neratinib versus 23 (1.6%) and 0 patients with placebo, respectively. In the neratinib group, 28.6% of patients had grade 3 events during month 1 decreasing to ≤ 6% after month 3. The median cumulative duration of grade 3/4 diarrhea with neratinib was 5 days (interquartile range, 2-9). Serious diarrheal events (n = 22, 1.6%) and diarrheal events requiring hospitalization (n = 20, 1.4%) were rare with neratinib. Changes in FACT-B total score by diarrhea grade in the neratinib group did not meet the threshold for clinically important differences. Conclusions: In the absence of antidiarrheal prophylaxis, neratinib-related diarrhea is short-lived and not associated with complications or long-term sequelae. This suggests that targeted preventive management with antidiarrheal prophylaxis early during neratinib treatment is appropriate. Trial registration: ClinicalTrials.gov NCT00878709. Registered 9 April 2009.
KW - Diarrhea
KW - Early-stage breast cancer
KW - HER2 positive
KW - Health-related quality of life
KW - Neratinib
KW - Pan-HER inhibition
KW - Patient-reported outcomes
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UR - http://www.scopus.com/inward/citedby.url?scp=85062212184&partnerID=8YFLogxK
U2 - 10.1186/s13058-019-1112-5
DO - 10.1186/s13058-019-1112-5
M3 - Article
C2 - 30813966
AN - SCOPUS:85062212184
VL - 21
JO - Breast Cancer Research
JF - Breast Cancer Research
SN - 1465-5411
IS - 1
M1 - 32
ER -