Phase III Trial Results Comparing Lymphoseek with Blue Dye in Detection of the Sentinel Lymph Node in Breast Cancer.

Abstract

Abstract Background: Lymphoseek (99mTc-DTPA–mannosyl-dextran) is a novel radiopharmaceutical specifically designed for intra-operative sentinel lymph node (SLN) detection. It is the first radiopharmaceutical to target lymphatic tissue by a specific molecular interaction of the drug with receptors found on macrophages. We report the results of a multi-center, open-label within-patient comparative study of Lymphoseek and vital blue dye in the detection of sentinel lymph nodes in patients with known breast cancer.Materials and Methods: A phase III clinical trial was conducted. The protocol received the consent of the Food and Drug Administration as well as the institutional review boards of each enrolling institution. Patients with known breast cancer were screened. Entrance criteria were age >18, ECOG= 0-2, clinically negative nodes, non-pregnant status. Exclusion criteria were metastatic disease, bilateral breast cancer, need for bilateral mastectomy, reduction mammaplasty, previous axillary basin surgery or irradiation. Each patient provided written informed consent.Baseline labs and electrocardiograms were performed for each patient. Patients underwent intra-operative SLN mapping with 0.5- 1.0 mCi of Lymphoseek and blue dye. Surgery was performed to identify the SLN. The primary objective of efficacy was the concordance between Lymphoseek and vital blue dye in the in-vivo detection of the excised lymph node(s) as confirmed by pathology. The requirements for designating a lymph node as identified by Lymphoseek were: >50 counts per 2 seconds, lymph nodes containing >3 standard deviations of the mean background counts or nodes containing >10% of the activity of the hottest node. All identified SLNs were removed for analysis, disease free SLNs were subjected to enhanced pathologic evaluation. Follow-up safety labs, electrocardiograms and physical examinations were performed 6-30 hours post injection. All patients were monitored for adverse events.Results: A total of 8 centers participated in the trial and consented 77 female patients (age 31-78 years) for enrollment into the trial. Of the 71 patients who met all entrance criteria and went on to lymphatic mapping surgery, 131 SLNs (mean 1.8) were identified by Lymphoseek and 94 (mean 1.3) were identified by blue dye. There were 13 positive axillary basins (18%), all of which were identified by Lymphoseek. Overall concordance rate of Lymphoseek with blue dye was 98%. There were 68 adverse events (4 serious); none were attributed to the study drug.Discussion: The primary endpoint, in-vivo concordance of Lymphoseek with blue dye in the detection of the SLN was achieved with a 98% concordance rate. The high in-vivo concordance rate demonstrates Lymphoseek's ability to detect SLNs when compared to the “gold standard” treatment. In addition, Lymphoseek correctly identified metastatic disease in all of the 13 axillary basins containing disease and did so while demonstrating an acceptable safety profile throughout the study. No adverse events were considered to be due to the administration of the study drug. The use of Lymphoseek, the first in-kind agent specifically designed for lymph node mapping, was validated as safe and effective in this multi-center phase III trial. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 304.