Category "viewpoints and debates" Is trastuzumab as a single agent obsolete in early breast cancer? Yes.

In 2005, two adjuvant trials revolutionised breast cancer treatment demonstrating a 50% reduction in relapses when trastuzumab was added to adjuvant chemotherapy. In order to improve further on these results three large phase III trials were conducted. ALTTO trial evaluated lapatinib. This trial was negative and lapatinib was quite toxic. ExteNET trial evaluated neratinib in patients who already had completed adjuvant treatment with trastuzumab. Neratinib reduced the risk of relapse by 27% and the drug is FDA approved. However 40% of patients experienced grade 3 diarrhoea and this toxicity profile will be an issue in daily practice. APHINITY trial evaluated a combination of pertuzumab and trastuzumab. Pertuzumab reduced the risk of relapse by 19% with a good toxicity profile. However the absolute invasive disease-free survival (IDFS) benefit at 4 years was only 1.7%. Despite this modest absolute benefit we believe that pertuzumab should be added to trastuzumab at least in two indications: first, in patients with node positive breast cancer, in whom the absolute IDFS benefit is 3.2% and qualify for a high clinical benefit based on ESMO magnitude of clinical benefit scale; second, in patients suitable for neoadjuvant chemotherapy. In this group, the absolute IDFS benefit could be estimated as high as 7% (starting pertuzumab in the neoadjuvant setting and following it in the adjuvant setting up to a total of 18 injections). Our arguments are developed in this viewpoint. Pertuzumab is approved in these two indications by FDA and EMA.