Does neratinib plus capecitabine benefit patients with heavily treated HER2-positive metastatic breast cancer?

This trial compared the effectiveness of neratinib (Nerlynx) plus capecitabine (Xeloda) in treating metastatic breast cancer compared to lapatinib (Tykerb) plus capecitabine in patients who have received 2 or more treatment lines. The authors found that neratinib plus capecitabine (N+C) resulted in improved survival without cancer worsening when compared to lapatinib plus capecitabine (L+C).

Breast cancer (BC) remains the most common form of cancer found in women worldwide. Some cancer expresses a protein called human epidermal growth factor receptor 2 (HER2). This BC is called HER2-positive (+) BC. This protein helps BC cells to grow. Lapatinib (L) is a targeted therapy that blocks HER2 and stops BC growth. Capecitabine (C) is a chemotherapy medication used to treat BC. L+C has been approved for HER2+ metastatic BC (MBC) in patients who have received previous treatment. 

Neratinib is also a targeted therapy approved for patients with HER2+ BC. Neratinib plus capecitabine (N+C) has shown effectiveness in treating patients with early-stage HER2+ BC. However, the safety and effectiveness of this combination in patients with MBC that have previously received 2 or more treatments remain under investigation.

There were 621 patients with metastatic HER2+ BC in this trial. 307 patients were randomly assigned to receive N+C. 314 patients were randomly assigned to receive L+C. The follow-up duration was 29.9 months.

Survival without cancer worsening was improved in the N+C group by 24% when compared with the L+C group. Significantly fewer patients in the N+C group needed interventions for brain disease (22.8%) compared to the L+C group (29.2%). 

Slightly more patients in the N+C group responded to treatment (32.8%) compared to the L+C group (26.7%). Response to N+C lasted significantly longer (8.5 months) compared to the response to L+C (5.6 months).

The most common side effects to treatment were diarrhea (83% with N+C vs 66% with L+C) and nausea (53% with N+C vs 42% with L+C).

The authors of this study concluded that neratinib plus capecitabine improved survival without cancer worsening and time to brain complications in patients with metastatic HER2+ BC.

This study was sponsored by Puma Biotechnology, the manufacturers of neratinib. This study served as basis for the approval of neratinib and capecitabine for patients with metastatic HER2+ BC that have previously received 2 or more treatments.