@article{707343d9e57f48efb76ecb5806e2d429,
title = "HALT-D: a randomized open-label phase II study of crofelemer for the prevention of chemotherapy-induced diarrhea in patients with HER2-positive breast cancer receiving trastuzumab, pertuzumab, and a taxane",
abstract = "Purpose: To assess whether crofelemer would prevent chemotherapy-induced diarrhea (CID) diarrhea in patients with HER2-positive, any-stage breast cancer receiving trastuzumab (H), pertuzumab (P), and a taxane (T; docetaxel or paclitaxel), with/without carboplatin (C; always combined with docetaxel rather than paclitaxel). Methods: Patients scheduled to receive ≥ 3 consecutive TCHP/THP cycles were randomized to crofelemer 125 mg orally twice daily during chemotherapy cycles 1 and 2 or no scheduled prophylactic medication (control). All received standard breakthrough antidiarrheal medication (BTAD) as needed. The primary endpoint was incidence of any-grade CID for ≥ 2 consecutive days. Secondary endpoints were incidence of all-grade and grade 3/4 CID by cycle/stratum; time to onset and duration of CID; stool consistency; use of BTAD; and quality of life (Functional Assessment of Chronic Illness Therapy for Patients With Diarrhea [FACIT-D] score). Results: Fifty-one patients were randomized to crofelemer (n = 26) or control (n = 25). There was no statistically significant difference between arms for the primary endpoint; however, incidence of grade ≥ 2 CID was reduced with crofelemer vs control (19.2% vs 24.0% in cycle 1; 8.0% vs 39.1%, in cycle 2). Patients receiving crofelemer were 1.8 times more likely to see their diarrhea resolved and had less frequent watery diarrhea. Conclusion: Despite the choice of primary endpoint being insensitive, crofelemer reduced the incidence and severity of CID in patients with HER2-positive breast cancer receiving P-based therapy. These data are supportive of further testing of crofelemer in CID. Trial registration: Clinicaltrials.gov, NCT02910219, prospectively registered September 21, 2016.",
keywords = "Chemotherapy-induced diarrhea, Crofelemer, HER2-positive breast cancer, Pertuzumab, Taxane, Trastuzumab",
author = "Pohlmann, {Paula R.} and Deena Graham and Tianmin Wu and Yvonne Ottaviano and Mahsa Mohebtash and Shweta Kurian and Donna McNamara and Filipa Lynce and Robert Warren and Asma Dilawari and Suman Rao and Candace Mainor and Nicole Swanson and Ming Tan and Claudine Isaacs and Swain, {Sandra M.}",
note = "Funding Information: This work was supported by Genentech, Inc., a member of the Roche group (Funding), Napo Pharmaceuticals, Inc. (provided crofelemer), and the Biostatistics and Biomedical Informatics Shared Resource of the Georgetown Lombardi Comprehensive Cancer Center (Grant Number NIH P30-CA051008). The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Funding Information: This study was supported by Genentech, Inc., a member of the Roche group (funding), and Napo Pharmaceuticals, Inc. (provided crofelemer). This research was supported by the Biostatistics and Biomedical Informatics Shared Resource of the Georgetown Lombardi Comprehensive Cancer Center (P30-CA051008). Napo Pharmaceuticals, Inc. acknowledges the contributions of the indigenous people of the Northwest Amazonian region in the development of crofelemer. We would also like to acknowledge Dr Jennifer Gao who participated in the design of the study during her National Cancer Institute oncology fellowship. Support for third-party editorial assistance for this manuscript, furnished by Daniel Clyde, PhD, of Health Interactions, was provided by Genentech, Inc. Funding Information: This study was supported by Genentech, Inc., a member of the Roche group (funding), and Napo Pharmaceuticals, Inc. (provided crofelemer). This research was supported by the Biostatistics and Biomedical Informatics Shared Resource of the Georgetown Lombardi Comprehensive Cancer Center (P30-CA051008). Napo Pharmaceuticals, Inc. acknowledges the contributions of the indigenous people of the Northwest Amazonian region in the development of crofelemer. We would also like to acknowledge Dr Jennifer Gao who participated in the design of the study during her National Cancer Institute oncology fellowship. Support for third-party editorial assistance for this manuscript, furnished by Daniel Clyde, PhD, of Health Interactions, was provided by Genentech, Inc. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1007/s10549-022-06743-9",
language = "English (US)",
volume = "196",
pages = "571--581",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",
number = "3",
}