The EMILIA study is a randomized, open-label, international trial involving patients with HER2-positive, unresectable, locally advanced or metastatic breast cancer who were previously treated with trastuzumab and a taxane. The study was conducted in accordance with the International Conference on Harmonization Good Clinical Practice standards and the Declaration of Helsinki. Patients provided written informed consent; the study was approved by the relevant institutional review board or independent ethics committee.
Patients were randomly assigned in a 1:1 ratio to T-DM1 or lapatinib plus capecitabine with the use of a hierarchical, dynamic randomization scheme through an interactive voice-response system. Stratification factors were world region (United States, Western Europe, or other), the number of prior chemotherapy regimens for unresectable, locally advanced or metastatic disease (0 or 1 vs. >1), and disease involvement (visceral vs. nonvisceral).
The primary end points were progression-free survival assessed by independent review, overall survival, and safety. Progression-free survival was defined as the time from randomization to progression or death from any cause. Progression was assessed according to modified Response Evaluation Criteria in Solid Tumors (RECIST), version 1.012 (link); the modified criteria are specified in theSupplementary Appendix , available with the full text of this article at NEJM.org . Overall survival was defined as the time from randomization to death from any cause. Prespecified secondary end points included progression-free survival (investigator-assessed), the objective response rate, the duration of response, and the time to symptom progression. The objective response rate was determined according to modified RECIST on the basis of an independent review of patients with measurable disease at baseline; responses were confirmed at least 28 days after the initial documentation of a response. The time to symptom progression was defined as the time from randomization to the first decrease of 5 points or more from baseline scores on the Trial Outcome Index of the patient-reported Functional Assessment of Cancer Therapy–Breast (FACT-B TOI, on which scores range from 0 to 92, with higher scores indicating a better quality of life)13 (link) in women with a baseline score and at least one postbaseline score. Safety was monitored by an independent data monitoring committee and a cardiac review committee.
Patients were randomly assigned in a 1:1 ratio to T-DM1 or lapatinib plus capecitabine with the use of a hierarchical, dynamic randomization scheme through an interactive voice-response system. Stratification factors were world region (United States, Western Europe, or other), the number of prior chemotherapy regimens for unresectable, locally advanced or metastatic disease (0 or 1 vs. >1), and disease involvement (visceral vs. nonvisceral).
The primary end points were progression-free survival assessed by independent review, overall survival, and safety. Progression-free survival was defined as the time from randomization to progression or death from any cause. Progression was assessed according to modified Response Evaluation Criteria in Solid Tumors (RECIST), version 1.012 (link); the modified criteria are specified in the
