Oral neratinib: Phase II data

Data from 40 HER2-positive breast cancer patients with progressive brain metastases in the first cohort of the open-label, U.S. Phase II TBCRC 022 trial showed that once-daily 240 mg oral neratinib led to 3 partial responses, 4 cases of stable disease for >=6 months and 12 cases of stable disease for <6 months. Median PFS was 1.9 months and median OS was 8.7 months. The most common severe adverse event reported was diarrhea. In the first 12 patients treated in the cohort, no prophylactic treatment with the antidiarrheal agent loperamide was given. Of these 12 patients, 29% experienced grade >=3 diarrhea and 25% experienced grade 2 diarrhea. In the next 28 patients treated in the cohort who also received low doses of loperamide, the rate of grade >=3 diarrhea was 21% and the rate of grade 2 diarrhea was 12%.

All patients in the first cohort had received prior radiotherapy, with 38% receiving prior whole brain radiotherapy alone, 23% receiving prior stereotactic radiosurgery alone and 40% receiving both. Additionally, 85% of patients in the first cohort received prior treatment with lapatinib and 83% received >=2 prior lines of chemotherapy in the metastatic setting. The trial was sponsored by the Dana-Farber Cancer Institute. Data were presented at the American Society of Clinical Oncology meeting in Chicago. ...