Improving the tolerability of neratinib in patients with early-stage HER2-positive breast cancer.

This trial evaluated strategies to improve diarrhea as a side effect of neratinib (Nerlynx) treatment in patients with HER2-positive breast cancer (BC). The authors showed that slowly increasing the doses of neratinib or taking anti-diarrhea medication can improve this side effect.

Neratinib (Nerlynx) is a targeted therapy approved for the treatment of HER2-positive BC. Previous trials have shown that 40% of patients developed diarrhea. This side effect can be severe and often results in stopping treatment.

Loperamide (Imodium) is a drug used in the prevention or treatment of diarrhea. Budesonide (Pulmicort) is a corticosteroid (steroid hormone) used in Crohn's disease (an inflammatory disease of the lining of the intestine associated with diarrhea and pain). Colestipol (Colestid) is a cholesterol-lowering drug that is also prescribed for diarrhea. It was unknown if administering any anti-diarrhea medication would reduce the occurrence of diarrhea in patients with early HER2-positive BC treated with neratinib.

There were 501 patients with early-stage HER2-positive BC in this trial. All patients had received previously trastuzumab (Herceptin) treatment. Trastuzumab is a targeted therapy used in HER2-positive BC. All patients received neratinib treatment for 1 year. Patients were separated into 5 groups. Group also received oral loperamide. Group 2 received budesonide and loperamide. Group 3 received colestipol and loperamide. Group 4 received colestipol and loperamide as needed. Group 5 received neratinib in increasing doses, without any anti-diarrhea medication. These patients were compared to patients in the original neratinib study, where no measurements were taken to prevent diarrhea.  

Severe diarrhea occurred less frequent compared to the original neratinib study. Severe diarrhea occurred in 31% of group 1, 28% of group 2, 21% of group 3, 32% of group 4 and 15% of group 5. This was compared to 40% of the original neratinib study. The proportion of patients who stopped treatment due to diarrhea was 20% in group 1, 8% in group 2, 4% in group 3, 8% in group 4, and 3% in group 5. This was compared to 17% in the original neratinib study.

Most episodes of diarrhea occurred in the first month of treatment. Most patients stopped treatment due to this side effect during the first month of treatment. 

The authors concluded that neratinib tolerability was improved with the use of anti-diarrheal medication or increasing doses. 

This study was supported by Puma Biotechnology, the manufacturer of neratinib. This trial compared results with the original neratinib trial but did not actually have a control group. This might have influenced the results.

If you have concerns about the side effects of neratinib treatment, please discuss this with your doctor.