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An Open-Label Study to Characterize the Incidence and Severity of Diarrhea in Patients with Early-Stage HER2+ Breast Cancer Treated with Neratinib and Intensive Loperamide Prophylaxis
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Diarrhea in ExteNET Trial
1 2 3 4 5 6 7 8 9 10 11 12
Pts with events 1310 692 615 569 513 490 453 413 437 414 392 366
Pts at risk 1408 1146 1074 1033 1006 971 935 924 911 888 873 863
95.4% All Grade (Grade 1-4) diarrhea
39.9% Grade 3 (or higher) diarrhea
Median duration of Grade 3 diarrhea: 5 days
of patients hospitalized due to diarrhea
26.4% of patients requiring dose reduction
16.8% of patients discontinuing neratinib due
No prophylaxis with loperamide given
ExteNET to prevent neratinib-related diarrhea
Neratinib-Diarrhea Prophylaxis with Loperamide in Metastatic Cancer
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Phase II Open-Label Study to Characterize the Incidence and Severity of Diarrhea in Patients with Early-Stage HER2+ Breast Cancer Treated with Neratinib and Intensive Loperamide
Goal: Investigate the use of loperamide given prophylactically to reduce neratinib related
diarrhea in patients treated for extended adjuvant HER2 positive breast cancer
Study Schema and Status
Patients enter study
within 1 year of completing adjuvant trastuzumab therapy (analogous to ExteNET population) Other prior HER2+ (neo) adjuvant therapy is permitted
Early HER2+ Breast Cancer
Received up to 1 year
of adjuvant trastuzumab
HR (ER/PR) positive or negative
Enrollment: 72 patients as of
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Original Protocol (n=27)
Day 1 : 16 mg/day (4 mg starting dose + 4 mg tid) Days 2-3: 12 mg/day (4 mg tid) Days 4-56 : 6-8mg/day (2 mg
Amended Protocol (n=23)
Days 1-14: 12 mg/day (4 mg tid) Day 15-56: 8 mg/day (4 mg bid)
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Study Preliminary Results
Patient Characteristics
4 (14.8%) 10 (43.5%) 14 (28%)
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Incidence of Grade 3 Treatment-emergent Diarrhea
Original Protocol Amendment 1 Total
Patients with events n
Grade 3 Diarrhea 5 (18.5) 3 (13.0) 8 (16.0)
Incidence of Grade 3
18.5% (6.3, 38.1) 13.0% (2.8, 33.6) 16.0% (7.2, 29.1)
with Loperamide 3/5 (60%) 2/3 (67%) 5/8 (63%)
No patients developed grade 4 diarrhea
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Characteristics of Treatment-emergent Diarrhea
Original Protocol Amendment 1 Total
(74.1) 10 (43.5) 30 (60.0)
Grade 3 5 (18.5) 3 (13.0) 8 (16.0)
Hospitalizations 0 (0.0) 0 (0.0) 0 (0.0)
9 (33.3) 6 (26.1) 15 (30.0)
0 (0.0) 1 (4.3) 1 (2.0)
2 (7.4) 1 (4.3) 3 (6.0)
Discontinued neratinib
7 (25.9) 1 (4.3) 8 (16.0)
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Treatment-emergent Diarrhea by Treatment Cycle
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Duration of Treatment-emergent Diarrhea
Protocol Amendment 1 Total
Duration of any grade (grade 1-3) diarrhea (days)
Duration of grade 3 diarrhea
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Based on preliminary results
in patients receiving loperamide prophylaxis, the estimated frequency of all grade diarrhea is 60% and grade 3 diarrhea is 16%
- Estimated frequency of all grade diarrhea for original protocol is 74.1% and grade 3 diarrhea is 18.5%
- Estimated frequency of all grade diarrhea for Amendment 1 is 43.5% and grade 3 diarrhea is 13.0%
- For comparison, in ExteNET (where no loperamide prophylaxis was given) all grade diarrhea was 95.4% and grade 3 diarrhea 39.8%
Grade 3 diarrhea appears limited to first 28 days (cycle 1) with the majority occurring the first week
All grade and grade 3 diarrhea when using loperamide prophylaxis appears to be short-term and not chronic. There were no
hospital admissions requiring IV fluids suggesting that the neratinib related diarrhea is acute, manageable and self-limiting
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Continue following additional
patients in Amendment 1 cohort
Report additional results (n=72) in 2016
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