LOS ANGELES--(BUSINESS WIRE)--Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company, announced that interim results from a Phase II clinical trial of Puma’s investigational drug PB272 (neratinib) were presented at the 2016 CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas. The presentation entitled, “Incidence and severity of diarrhea with neratinib plus intensive loperamide prophylaxis in patients with HER2-positive early-stage breast cancer (EBC): Interim analysis from the multicenter, open-label, phase II CONTROL trial” was presented as a poster presentation.
“We are pleased to see the reductions in the incidence of severe neratinib-related diarrhea in the CONTROL trial when using the loperamide and/or loperamide plus budesonide combination. We are further pleased to see the severe diarrhea become more acute, whereby it does not typically recur after the first month.”
The main adverse event that has been seen to date in clinical trials of neratinib is diarrhea and more specifically grade 3 diarrhea. In the Phase III ExteNET trial of neratinib as extended adjuvant treatment of HER2-positive early stage breast cancer that has previously been treated with adjuvant Herceptin, 95.4% of the patients experienced all grade diarrhea and 39.8% of the patients experienced grade 3 or higher diarrhea (there was one event of grade 4 diarrhea). The CONTROL trial is an international, open-label, phase II study investigating the use of loperamide prophylaxis with or without other agents in the prevention and reduction of neratinib-associated diarrhea and more specifically grade 3 diarrhea.
In the trial, patients with HER2-positive early-stage breast cancer who had completed trastuzumab-based adjuvant therapy received neratinib daily for a period of one year. High dose loperamide prophylaxis was given for the first 2 cycles (56 days) of treatment. Initially, the loperamide dosing used was 16 mg on day 1, then 12 mg on days 2 and 3 and then 6-8 mg on days 4-56 (original dosing). The protocol was later amended to simplify the regimen such that patients took 12 mg on days 1-14 and 8 mg on days 15-56 (modified dosing). The CONTROL trial has recently been expanded to include prophylaxis with the combination of loperamide and budesonide, a locally acting corticosteroid that the Company believes targets the inflammation identified in a preclinical model of neratinib-induced diarrhea.
The interim analysis of the trial presented in the poster included a total of 135 patients who received neratinib plus loperamide prophylaxis (28 patients taking the original dosing and 107 patients taking the modified dosing) and 40 patients who received neratinib plus loperamide prophylaxis for 2 cycles and budesonide for 1 cycle.
The results of the trial showed that the incidence of grade 3 diarrhea for the total 135 patients who received the loperamide prophylaxis was 28.1%. For the 28 patients who received loperamide using the original dosing regimen the grade 3 diarrhea rate was 25.0% and for the 107 patients who received the modified loperamide dosing regimen the grade 3 diarrhea rate was 29.0%. For the patients in the original dosing group, 71% of the patients who experienced grade 3 diarrhea were known to be non-compliant with the loperamide regimen and for the patients in the modified loperamide dosing regimen, 35% of the patients were known to be non-compliant with their loperamide dosing regimen. For the 135 patients who received the loperamide prophylaxis, the median number of grade 3 diarrhea episodes per patient was 1 and the median cumulative duration of grade 3 diarrhea was 3 days. For the 135 patients who received loperamide prophylaxis, 18.5% discontinued neratinib due to diarrhea.
For the 40 patients who received the combination of loperamide plus budesonide, the results of the trial showed that the incidence of grade 3 diarrhea was 15.0%. None of the patients who experienced grade 3 diarrhea were non-compliant with the loperamide plus budesonide regimen. The median number of grade 3 diarrhea episodes per patient was 1 and the median cumulative duration of grade 3 diarrhea was 2.5 days. For the 40 patients who received loperamide plus budesonide prophylaxis, 5.0% discontinued neratinib due to diarrhea. Further information is provided in Table 1 below:
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