Making Sense of Dual HER2-Targeting in Early Breast Cancer?
A partir de données d'essais cliniques ayant inclus 2 247 patientes atteintes d'un cancer du sein HER2+, cette méta-analyse en réseau évalue l'efficacité et la toxicité de divers traitements néoadjuvants comprenant du trastuzumab, du lapatinib ou du pertuzumab
Human epidermal growth factor receptor 2 (HER2)–positive breast cancer has become one of the most treatable forms of the disease, with four FDA-approved anti-HER2 therapies (trastuzumab, lapatinib, pertuzumab, and trastuzumab emtansine) and multiple options for combining and sequencing these drugs in the metastatic setting. Dual HER2 targeting using the small molecule HER1/HER2 inhibitor lapatinib or the HER2 heterodimerization domain monoclonal antibody pertuzumab added to the anti-HER2 antibody trastuzumab improves overall survival compared with HER2 targeting using any single agent in the metastatic setting (1,2). A similar role of dual-agent HER2 targeting in preventing relapses in nonmetastatic HER2-positive breast cancer is the objective of several clinical trials in the nonmetastatic setting.
Given the expense, size, and time required for adjuvant trials, it is increasingly popular to use the neoadjuvant approach, in which the same drugs are given preoperatively and response is measured by pathologic complete response (pCR) to therapy as an intermediate biomarker for relapse-free and overall survival. This approach is justified by the unequivocal relationship of pCR to outcome (3) and is the reason that the US Food and Drug Administration (FDA) has endorsed neoadjuvant trials for registrational strategies. In 2012, the FDA granted accelerated approval of pertuzumab added to neoadjuvant chemotherapy plus trastuzumab based on a neoadjuvant trial demonstrating statistically significantly increased pCR, NeoSPHERE (4); this approval subsequently resulted in the National Comprehensive Cancer Network endorsement of pertuzumab in the …
Journal of the National Cancer Institute , éditorial, 2014