Pertuzumab, a monoclonal antibody, has been licensed in the US for the treatment of patients with HER2+ metastatic Breast Cancer (BC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease by June 2012. In Europe, market application has been submitted and is currently under review.
The FDA's decision for granting market authorisation was based on a phase III trial, which had enrolled 808 patients with HER2+ metastatic BC who had not been treated for their metastatic disease. The combination of trastuzumab and docetaxel in addition to pertuzumab was compared to placebo with trastuzumab and docetaxel. Within this trial, progression-free survival, the primary outcome, was improved by 6.1 months in the pertuzumab group in comparison to placebo. Mature results for Overall Survival were not yet available, but response rates were also superior.
The most common adverse event of higher grade (i.e. grade ≥3) was neutropenia in both groups (I 49% vs C 46%). Other frequently observed side-effects of higher grades in the pertuzumab group were febrile neutropenia and diarrhoea.
However, only the minority of patients (i.e. 10%) enrolled in the phase III trial had been previously treated with (neo-)adjuvant trastuzumab, a regimen commonly used for HER2+ breast cancer in the adjuvant setting. Thus, the study population differs from those patients who will be treated in daily practice.
Due to a clinically relevant gain in Progression-Free Survival and tolerable side-effects, the combination of pertuzumab + trastuzumab + docetaxel has already been incorporated into some guidelines. Even though no cost estimates are available for Austria, evidence indicates that pertuzumab will be a costly drug, producing expenses that will have to be added to those of trastuzumab and docetaxel.