Multicenter phase 2 trial of neratinib plus trastuzumab emtansine for HER2-positive breast cancer with brain metastases

Cohort 4 of the multicenter phase 2 trial 022 by the Translational Breast Cancer Research Consortium evaluated the combination of neratinib plus trastuzumab emtansine (T-DM1) for HER2-positive breast cancer brain metastases (BCBMs). Patients were included in three groups: group 4A consisted of patients with previously untreated BCBMs, group 4B included patients with treated BCBMs not previously exposed to T-DM1, and group 4 C consisted of patients with BCBMs previously exposed to T-DM1. The CNS objective response rate was 33.3% in group 4A, 35.3% in group 4B, and 28.6% in group 4C. Diarrhea was the most common grade 3 toxicity (22.7% of patients). The median overall survival was 30.2 months in group 4A, 23.3 months in group 4B, and 20.9 months in group 4C. The authors conclude that the combination of neratinib and T-DM1 had intracranial activity, including in patients previously exposed to T-DM1, suggesting synergy of both agents.