Neratinib in the early-stage/extended adjuvant breast cancer patient.

Breast cancer is the most common tumor type observed in women in the United States. The majority of patients are diagnosed at an early stage, but the disease often recurs after initial treatment. Human epidermal growth factor receptor 2 (HER2) gene amplification is present in approximately 20% to 25% of breast tumors and is associated with invasive disease and an aggressive phenotype. The addition of anti-HER2 therapy to chemotherapy has significantly improved the prognosis for patients with these aggressive tumors. However, despite the dramatic advances in survival achieved by targeting HER2, patients with these tumors are still at risk for recurrence after initial treatment. In an effort to address the risk for recurrence, recent clinical trials have evaluated the efficacy and safety of anti-HER2 antibodies and HER2 tyrosine kinase inhibitors as adjuvant or extended adjuvant therapy. Meaningful reductions have been observed in the risk for invasive and distant recurrence, particularly in certain HER2-positive breast cancer subpopulations. To optimize adjuvant treatment, therapies should be prescribed for patient subpopulations based on factors such as underlying risk profile, response to initial therapy, and patient preference. Neratinib is a small-molecule, irreversible tyrosine kinase inhibitor of HER1, HER2, and HER4 that penetrates the blood-brain barrier. This monograph examines neratinib in the setting of early-stage/extended adjuvant breast cancer, with a focus on clinical trial data, the mechanism of action, and ways to optimize clinical use.