Neratinib administered to patients with early stage HER2-positive breast cancer after trastuzumab-based adjuvant therapy for 12 months significantly improved 2-year invasive disease-free survival.1
A total of 2840 women with stage 1 to 3 HER2-positive breast cancer who had completed neoadjuvant and adjuvant trastuzumab therapy up to 1 year prior to randomization were randomly assigned to receive oral neratinib 240 mg per day (n = 1420) or matching placebo (n = 1420). The primary endpoint of this randomized placebo-controlled phase 3 trial was invasive disease-free survival 2 years following randomization.
Results showed that at a median 2-year follow-up, there were 70 invasive disease-free survival events in the neratinib group compared with 109 in the placebo group (stratified HR, 0.67; 95% CI, 0.50 – 0.91; P = .0091). Two-year invasive disease-free survival rate was 93.9% for neratinib vs 91.6%; 95% CI, 92.4 – 95.2; 95% CI, 90.0 – 93.0, respectively)
Serious adverse events occurred in 7% of patients in the neratinib group vs 6% of patients in the placebo group. The most common grade 3/4 adverse events for patients in the neratinib group were diarrhea (grade 3, 40%; grade 4 < 1% vs 2% grade 3 for placebo), vomiting (grade 3, 3% vs < 1%, respectively) and nausea (grade 3, 2% vs < 1%, respectively). QT prolongation occurred in 3% of patients in the neratinib group vs 7% in the placebo group.
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Seven deaths unrelated to disease progression or treatment occurred after study discontinuation (4, neratinib; 3 placebo). The causes of death for patients receiving neratinib were unknown in 2 patients, a second brain tumor in 1 patient, and acute myeloid leukemia in 1 patient. In the placebo group, causes of death were a brain hemorrhage in 1 patient, myocardial infarction in 1 patient, and gastric cancer in 1 patient.
Investigators concluded that longer follow-up is required to ensure that improvement in outcome is maintained.
- Chan A, Delaloge S, Holmes FA, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial [published online ahead of print February 10, 2016]. Lancet Oncol. doi: 10.1016/S1470-2045(15)00551-3.