Jaguar Health Announces Topline Results of Investigator-Initiated Phase 2 Study of Crofelemer for Prevention of Chemotherapy-Induced Diarrhea (CID) in Breast Cancer Patients
Crofelemer is a novel, oral plant-based non-opioid antidiarrheal medication
As reported in the abstract (Publication Number: P5-18-09) posted by the San Antonio Breast Cancer Symposium (SABCS), the study included 51 breast cancer patients randomly assigned to either crofelemer or control standard of care with no prophylactic antidiarrheal medications. Findings showed that the primary endpoint - the incidence of having diarrhea for two or more days - was not statistically different for the two groups since about 70% of patients had this outcome regardless of cycle or CID treatment group, which is consistent with the experience of CID in patients receiving these chemotherapy regimens. The crofelemer group demonstrated better outcomes compared to the control group for a number of key secondary endpoints:1
- Lower incidence of grade 2 or higher-grade diarrhea for the crofelemer group compared to the control group during cycle 2, based on patient-reported outcomes: 9.0% vs. 33.3%.
- Lower incidence of grade 2 or higher-grade diarrhea for the crofelemer group compared to the control group during cycle 2, based on investigator assessments: 9.5% vs. 41.1%.
- No patients in the crofelemer group experienced grade 3 or grade 4 diarrhea during cycle 2 compared to 17.6% of patients in the control group, based on patient-reported outcomes.
"A number of findings of secondary endpoints were significantly in favor of crofelemer," said lead study investigator
"These are important findings for patients with CID and the physicians who treat them," said
The HALT-D study is separate from the
More About HALT-D1
The patients in the HALT-D trial were scheduled for at least three consecutive 21-day cycles of chemotherapy with THP (trastuzumab and pertuzumab with paclitaxel or docetaxel) or TCHP (docetaxel, carboplatin, trastuzumab and pertuzumab). Patients were randomized 1:1 to receive crofelemer during chemotherapy cycles 1 and 2, or standard-of-care with no prophylactic antidiarrheal therapy. All patients received breakthrough antidiarrheal medications as needed.
The primary endpoint was the incidence of any diarrhea (grades 1-4) for two or more consecutive days. Secondary endpoints included the incidence of any diarrhea and of severe diarrhea (grades 3 or 4), time to onset and duration of diarrhea, stool consistency, frequency of breakthrough antidiarrheal medication use, and quality-of-life measures. Data included physician assessments and patient-reported outcomes.
Full results for the secondary endpoints will be presented in the virtual and narrated poster available on the SABCS website and presented in person at the SABCS poster session from
The HALT-D study was sponsored and conducted by
About Chemotherapy-Induced Diarrhea
A significant proportion of patients undergoing cancer therapy experience diarrhea, and diarrhea has the potential to cause dehydration, potential infections, and non-adherence to treatment in this population. Novel "targeted cancer therapy" agents, such as epidermal growth factor receptor (EGFR) antibodies and tyrosine kinase inhibitors (TKIs), with or without cycle chemotherapy agents, may cause increased electrolyte and fluid content in the gut lumen, which results in passage of loose/watery stools (i.e., diarrhea). Diarrhea has been reported as one of the most common side effects of TKIs and may result in cancer therapy drug holidays or reductions from therapeutic dose, potentially impacting patient outcome. Diarrhea is also a common side effect of some approved CDK 4/6 inhibitors.
Crofelemer is a novel, oral plant-based medicine purified from the red bark sap, also referred to as "dragon's blood," of the medicinal Croton lechleri tree in the Amazon Rainforest. Napo has established a sustainable harvesting program, under fair trade practices, for crofelemer to ensure a high degree of quality, ecological integrity, and support for Indigenous communities. Crofelemer is the active ingredient in Mytesi®,
For more information about
Mytesi® (crofelemer delayed release tablets) is an antidiarrheal indicated for the symptomatic relief of noninfectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy (ART). Mytesi® is not indicated for the treatment of infectious diarrhea. Infectious etiologies of diarrhea should be ruled out by a physician before starting Mytesi®. If infectious etiologies are not considered, there is a risk that patients with infectious etiologies will not receive the appropriate therapy and their disease may worsen. In clinical studies, the most common adverse reactions occurring at a rate greater than placebo were upper respiratory tract infection (5.7%), bronchitis (3.9%), cough (3.5%), flatulence (3.1%), and increased bilirubin (3.1%).
More information and complete Prescribing Information are available at Mytesi.com.
Certain statements in this press release constitute "forward-looking statements." These include statements regarding
- Pohlmann PR, Graham D, Wu T, et al. HALT-D: A randomized open label phase 2 study of crofelemer for the prevention of chemotherapy induced diarrhea (cid) in patients with breast cancer receiving trastuzumab, pertuzumab, and a taxane. Abstract 2142 of poster presentation P5-18-09. Available sabcs.org (San Antonio Breast Cancer Symposium). Accessed
November 19, 2021.
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- Dang C, Iyengar N, Datko F, et al. Phase II study of paclitaxel given once per week along with trastuzumab and pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer [published correction appears in J Clin Oncol. 2019
Feb 1;37(4):354]. J Clin Oncol. 2015;33(5):442-447. doi:10.1200/JCO.2014.57.1745
- Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25-32. doi:10.1016/S1470-2045(11)70336-9
- Schneeweiss A, Chia S, Hickish T, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278-2284. doi:10.1093/annonc/mdt182