Questioning Our APHINITY for More
Mené sur 2 400 patientes atteintes d'un cancer du sein HER2+ de stade précoce et opérable, cet essai randomisé évalue l'efficacité, du point de vue de la survie sans maladie invasive à 3 ans, et la toxicité de l'ajout du pertuzumab au trastuzumab et à une chimiothérapie standard en traitement adjuvant
The initial report of the effect of human epidermal growth factor receptor 2 (HER2) amplification on the risk of relapse and death from breast cancer1 ushered in the modern world of “targeted” therapy, and research moved quickly from target identification to therapeutic exploitation. Trastuzumab, the first HER2-targeted monoclonal antibody, improved overall survival when added to chemotherapy for patients with HER2-positive metastatic disease.2 Adjuvant trials followed, with similarly impressive reductions in the risk of recurrence and death.3-5
Given the importance of HER2 as a therapeutic target, it is no surprise that other HER2-targeted agents soon followed. Pertuzumab has limited activity as a single agent in patients with trastuzumab-resistant disease. However, in the purest display of synergy, patients who had disease progression while receiving both trastuzumab and pertuzumab separately had a response to the combination.6 The addition of pertuzumab to trastuzumab and docetaxel was found to improve overall survival by 15.7 months,7 an absolute benefit that dwarfed the 4.8-month improvement obtained by adding trastuzumab to chemotherapy. For patients receiving neoadjuvant therapy, dual HER2 inhibition nearly doubled the rate of pathological complete response, leading to accelerated regulatory approval.8 Enthusiasm for dual inhibition was so rampant that the National Comprehensive Cancer Network (a group of 27 cancer centers that establish evidence-based cancer-treatment guidelines) abandoned their usual need for data and incorporated pertuzumab into adjuvant treatment recommendations.
The results of the APHINITY trial, in which pertuzumab was added to chemotherapy and trastuzumab in the context of adjuvant therapy, have now been reported in the Journal by von Minckwitz et al.9 The results with regard to the primary end point, invasive-disease–free survival, were significant. To be clear, APHINITY is a positive trial. To be equally clear, as compared with results of studies of pertuzumab in the context of metastatic disease and neoadjuvant therapy, APHINITY is a disappointment.
New England Journal of Medicine , éditorial en libre accès, 2016