Combined Analysis of Phase III Trials Evaluating [99mTc]Tilmanocept and Vital Blue Dye for Identification of Sentinel Lymph Nodes in Clinically Node-Negative Cutaneous Melanoma

Abstract

Background[99mTc]Tilmanocept is a CD206 receptor-targeted radiopharmaceutical designed for sentinel lymph node (SLN) identification. Two nearly identical nonrandomized phase III trials compared [99mTc]tilmanocept to vital blue dye.MethodsPatients received [99mTc]tilmanocept and blue dye. SLNs identified intraoperatively as radioactive and/or blue were excised and histologically examined. The primary end point, concordance, was the proportion of blue nodes detected by [99mTc]tilmanocept; 90 % concordance was the prespecified minimum concordance level. Reverse concordance, the proportion of radioactive nodes detected by blue dye, was also calculated. The prospective statistical plan combined the data from both trials.ResultsFifteen centers contributed 154 melanoma patients who were injected with both agents and were intraoperatively evaluated. Intraoperatively, 232 of 235 blue nodes were detected by [99mTc]tilmanocept, for 98.7 % concordance (p < 0.001). [99mTc]Tilmanocept detected 364 nodes, for 63.7 % reverse concordance (232 of 364 nodes). [99mTc]Tilmanocept detected at least one node in more patients (n = 150) than blue dye (n = 138, p = 0.002). In 135 of 138 patients with at least one blue node, all blue nodes were radioactive. Melanoma was identified in the SLNs of 22.1 % of patients; all 45 melanoma-positive SLNs were detected by [99mTc]tilmanocept, whereas blue dye detected only 36 (80 %) of 45 (p = 0.004). No positive SLNs were detected exclusively by blue dye. Four of 34 node-positive patients were identified only by [99mTc]tilmanocept, so 4 (2.6 %) of 154 patients were correctly staged only by [99mTc]tilmanocept. No serious adverse events were attributed to [99mTc]tilmanocept.Conclusions[99mTc]Tilmanocept met the prespecified concordance primary end point, identifying 98.7 % of blue nodes. It identified more SLNs in more patients, and identified more melanoma-containing nodes than blue dye.

99mTc-Tilmanocept: A Novel Molecular Agent for Lymphatic Mapping and Sentinel Lymph Node Localization

“…Melanoma was identified in the SLNs of 22.1% of patients. 99m Tc-tilmanocept identified more SLNs in more patients and identified more melanoma-containing nodes than VBD, with no serious adverse events attributed to 99m Tc-tilmanocept (24). A similar phase III study for SLN mapping was performed on breast cancer patients.…”

AACR Cancer Progress Report 2013

“…In March 2013, the FDA approved a new agent for locating lymph nodes in patients with breast cancer or melanoma who are undergoing surgery to remove sentinel lymph nodes. The agent, technetium Tc 99m tilmanocept (Lymphoseek), is a radioactive diagnostic imaging agent that was shown in two clinical trials to locate more sentinel lymph nodes in more patients compared with vital blue dye (156,157). Further, technetium Tc 99m tilmanocept identified more sentinel lymph nodes that were subsequently shown by routine pathology to contain cancer cells.…”

Optimization via specific fluorescence brightness of a receptor-targeted probe for optical imaging and positron emission tomography of sentinel lymph nodes

“…6 Technetium-99m-labeled tilmanocept, 7 also known as [ 99m Tc]-diethylenetriaminepentaacetic acid (DTPA)-mannosyldextran, 8 is a receptor-targeted radiopharmaceutical designed for SLN detection. Using an "instant kit" formulation 9 with the tradename Lymphoseek, a series of phase 1, 10,11 phase 2, 12 and phase 3 13,14 clinical trials, using intradermal, subareolar, and periturmoral administrations, demonstrated rapid SLN accumulation, high SLN retention, high concordance with vital blue dye, and no adverse events related to the radiopharmaceutical. Technetium-99m-labeled tilmanocept was approved for clinical use by the U.S. Food and Drug Administration in March 2013.…”