Before the advent of HER2-targeted therapies, the 20–25% of patients with breast tumors that overexpressed HER2 had a poor prognosis. The approval and use of the HER2-targeted monoclonal antibody trastuzumab has gone some way to ameliorating this problem; however, more treatment options are still needed.

One experimental therapy that might act in parallel with trastuzumab is another HER2-targeted monoclonal antibody, pertuzumab. This antibody targets a different area on the HER2 receptor to trastuzumab and so the rationale was that the two therapies would act in concert. A recent study (NeoSphere) has assessed the combination in the neoadjuvant setting in 417 treatment-naive patients with locally advanced, inflammatory or early stage HER2-positive breast cancer.

The patients were randomly assigned to one of four regimens: group A received trastuzumab and docetaxel; group B received pertuzumab, trastuzumab and docetaxel; group C received pertuzumab and trastuzumab; and group D received pertuzumab and docetaxel. The primary end point of the trial was pathological complete response in the breast, which was assessed at surgery after receiving four 3-weekly cycles of therapy. Importantly, this is a short time period over which to assess a clinically meaningful primary end point, a considerable advantage for carrying out clinical trials in this setting.

Patients in group B had a significantly improved pathological complete response rate than those in group A who were receiving the current therapy (45.8% versus 29.0%). Regimens A and B both achieved better results than the other two experimental arms (16.8% and 24.0% for arms C and D, respectively). The authors state that “importantly, the combination of pertuzumab with trastuzumab did not result in any additional safety signals” and that, therefore, “this triplet combination [trastuzumab, pertuzumab and docetaxel] could be an attractive proposition for patients with HER2-positive breast cancer.”

These data are being followed up in an ongoing phase III trial in the adjuvant setting (APHINITY), the results from this trial will be awaited with interest.