Evaluating the final effectiveness and safety outcomes of neratinib in patients with early stage HER2+/HR+ breast cancer.

This study reported the final effectiveness and safety outcomes of neratinib treatment in patients with early-stage HER2+/HR+ breast cancer. The data showed that neratinib significantly improved invasive disease-free survival in these patients who initiated treatment within 1 year of trastuzumab-based therapy.

BC is classified into different subtypes depending on the presence or absence of certain receptors (proteins found on the surface of the cancer cells). Hormone receptor (HR)-positive and HER2 positive is a subtype of BC that tests positive for both the hormone receptor and the HER2 protein. This type of cancer accounts for 15-20% of all BCs. Patients with this subtype of BC commonly receive targeted therapy such as trastuzumab (Herceptin).

Since the approval of the drug trastuzumab, the survival of patients with HER2+ early-stage BCs has improved dramatically. Trastuzumab locks onto HER2 and inhibits its actions. Neratinib (Nerlynx) is a targeted therapy that is also designed to inhibit HER2. It has been approved for use after the patient has already been treated with trastuzumab. However, the long-term effectiveness and safety of neratinib in patients with early-stage HER2+/HR+ BC already treated with trastuzumab is not known.

This study involved 2840 women with stage 1-3 HER2-positive BC that had received trastuzumab therapy and chemotherapy. Patients were randomly assigned to receive either neratinib (240 mg/day) or a placebo for 12 months. Patients were followed up for an average of 8 years.

1631 women of the population had HR-positive BC. 82% (1334) of these patients had started study treatment within 1 year of prior trastuzumab (group 1) and 18% (297) of the patients had started study treatment after 1 year of trastuzumab (group 2).

In group 1, 90.8% of those treated with neratinib and 85.7% of those treated with placebo were free of invasive disease after 5 years. In group 2, 93.0% of those treated with neratinib and 91.7% in those treated with a placebo were free of invasive BC. The benefits of neratinib were more pronounced for distant recurrences such as brain metastasis (cancer spread to the brain).

The estimated 8-year overall survival (OS) rates for group 1 were 91.5% in the neratinib group and 89.4% in the placebo group. The most common side effect reported in patients treated with neratinib was diarrhea.

This study concluded that neratinib significantly improved invasive disease-free survival in patients with HER2+/HR+ early-stage BC who initiated treatment within 1 year of prior trastuzumab.

This study was supported by Puma Biotechnology, the manufacturer of neratinib.