Neratinib Shows Some Activity in Previously Treated HER2-Positive Breast Cancer Brain Metastases
In the phase II Translational Breast Cancer Research Consortium (TBCRC) 022 study, reported by Freedman et al in the Journal of Clinical Oncology, the erbB1, HER2, erbB4 inhibitor neratinib showed some activity in patients with HER2-positive breast cancer brain metastases.
Study Details
In the study, 40 patients with central nervous system (CNS) progression after at least one line of CNS-directed therapy, including whole-brain radiotherapy, stereotactic radiosurgery, and surgical resection, received oral neratinib at 240 mg once daily, with tumors assessed at the end of every two 28-day cycles. The primary endpoint was composite CNS objective response rate, requiring ≥ 50% reduction in the volumetric sum of target CNS lesions and no progression of nontarget lesions, with no new lesions, systemic disease progression, clearly worsening neurologic status, or increase in corticosteroid dose. Overall, 78% of patients had previous whole-brain radiotherapy.
Responses
Partial response was achieved in three women (response rate = 8%, 95% confidence interval = 2%–22%), with the response rate not meeting the criterion for success (five responders). The median number of cycles received was two (range = one to seven), with five women receiving at least six cycles. Stable disease with ≥ 6 cycles occurred in 4 women (10%) and with < 6 cycles in 12 patients (30%). Among nine patients without previous whole-brain radiotherapy, one had partial response, and four had stable disease. Median progression-free survival was 1.9 months.
Adverse Events
The most common grade ≥ 3 adverse event was diarrhea, which occurred in 21% of patients taking prespecified loperamide prophylaxis and in 28% without prophylaxis. Dose reduction was required in six patients—three for diarrhea, two for nausea and diarrhea, and one for liver function abnormality.
The investigators concluded: “Although neratinib had low activity and did not meet our threshold for success, 12.5% of patients received six or more cycles. Studies combining neratinib with chemotherapy in patients with CNS disease are ongoing.”
The study was supported by the AVON Foundation, Breast Cancer Research Foundation, Susan G. Komen for the Cure, Dana-Farber Women’s Cancer Program Executive Council Personalized Medicine Award, Dana-Farber/Harvard Cancer Center, and Puma Biotechnology.
Rachel A. Freedman, MD, of Dana-Farber Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.
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