HER2-Directed Treatment of Metastatic Breast Cancer: Unanswered Questions

摘要

Drs. Jelovac and Emens have conducted a comprehen-sive review of human epidermal growth factor re-ceptor 2 (HER2)-targeted treatment for metastatic breastcancer. They have carefully reviewed the three availableclasses of agents-monoclonal antibodies, tyrosine kinaseinhibitors, and antibody-drug conjugates-and shown thateach has contributed to improved treatment of this disease.Prior to the advent of HER2-directed therapies,breast cancers with amplification of the HER2 gene wereassociated with significantly shorter disease-free survivalvs tumors without amplification. [1] Since the approvalof trastuzumab (Herceptin) in 1998 as the first HER2-directed therapy, the field has continued to develop rap-idly. In the pivotal trial in the first-line metastatic setting,addition of trastuzumab to chemotherapy increasedthe median overall survival (OS) from 20 months to 25months (P = .046), despite a 72% crossover rate. [2] Withthe recent approval in 2012 of pertuzumab (Perjeta) incombination with trastuzumab and docetaxel in the first-line setting, the median OS is expected to be substantial-ly longer. [3]_ In the most recent update of the CLEOPA-TRA trial, with a median follow-up of 30 months, themedian OS of patients on the three-drug combinationhad not yet been reached, as compared with 37.6 monthsOS for patients who received trastuzumab and docetaxel.[4] Risk of death was reduced by 34% for people whoreceived pertuzumab in addition to trastuzumab plusdocetaxel (HR = 0.66; P = .0008). Despite these ground-breaking advances, some unanswered questions remain.