Neratinib had low activity in patients with human epidermal growth factor receptor 2 (HER2)-positive breast brain metastases, but 12.5% of patients were able to receive 6 more cycles, a study published in the Journal of Clinical Oncology has shown.1

Because evidence-based treatments for metastatic HER2-positive breast cancer in the central nervous system (CNS) are limited, researchers sought to evaluate the activity and safety of neratinib. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, and had demonstrated promising activity in HER2-positive breast cancer.

For the open-label, phase 2 trial, researchers enrolled 40 patients with HER2-positive brain metastases who experienced disease progression in the CNS after 1 or more lines of CNS-directed therapy, such as stereotactic radiosurgery, surgical resection, and/or whole-brain radiotherapy.

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Of those, 78% had received previous whole-brain radiotherapy. All participants received neratinib 240 mg orally once daily, and had their tumors assessed every 2 cycles.

Results showed that the CNS objective response rate was 8% (95% CI, 2 – 22), or 3 partial responses. Median progression-free survival was 1.9 months.

Researchers also found that although the median number of cycles patients received was 2, 5 women received 6 or 7 cycles of neratinib.

The most grade 3 or higher adverse event was diarrhea, which occurred in 21% of patients taking loperamide prophylaxis and 28% of those not taking prophylaxis. Patients’ quality of life was also shown to have decreased over time.

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“Although neratinib had low activity and did not meet our threshold for success, 12.5% of patients received 6 or more cycles,” the authors concluded. “Studies combining neratinib with chemotherapy in patients with CNS disease are ongoing.”


  1. Freedman RA, Gelman RS, Wefel JS, et al. Translational Breast Cancer Research Consortium (TBCRC) 022: a phase ii trial of neratinib for patients with human epidermal growth factor receptor 2–positive breast cancer and brain metastases [published online ahead of print February 1, 2016]. J Clin Oncol. doi: 10.1200/JCO.2015.63.0343.