Neratinib in HER2-Positive Breast Cancer

The randomized ExteNET clinical trial evaluated neratinib in 2840 patients with HER2-positive, early stage breast cancer who had undergone surgery and received adjuvant trastuzumab. Patients who remained disease-free following 1 year of treatment with adjuvant trastuzumab and chemotherapy were randomized to neratinib (n = 1420) or placebo (n = 1420), notes Edith Perez, MD. The 2-year invasive DFS rate was 93.9% in the neratinib arm versus 91.6% with placebo, representing a 33% reduction in the risk of recurrence (hazard ratio [HR] = 0.67; P = .009).

In the phase III study, 95.4% of patients treated with neratinib experienced all-grade diarrhea (39.9% was grade 3/4), which requires proper management, Debu Tripathy, MD, explains. Based on early observations, the protocol was modified to use preventive measures for diarrhea, such as high dose loperamide. Prophylactic loperamide appears to make the side effect manageable, comments Carlos L. Arteaga, MD.

The phase II NEfERTT trial evaluated neratinib and paclitaxel versus trastuzumab and paclitaxel as first-line treatment in individuals with HER2-positive, locally recurrent or metastatic breast cancer. Treatment with paclitaxel in combination with neratinib reduced the incidence of brain metastases compared to those who received paclitaxel and trastuzumab, notes Joyce O’Shaughnessy, MD. Objective response rates (ORR) and progression-free survival (PFS) were similar between the two arms, while those treated with neratinib were 52.6% less likely to develop a CNS metastases.

Results of the ExteNET trial hinted that co-blockade of HER2 and hormone receptors may confer an even larger benefit than with either agent alone, Peresz notes. In clinical practace, hormonal therapy is generally reserved until chemotherapy is complete. Given the findings in the study, it could be worthwhile to explore concomitant hormonal therapy with chemotherapy, Perez notes.