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
[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.
Patients 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.
Fifteen 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.
[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.
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- 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
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Annals of Surgical Oncology
Volume 20, Issue 2 , pp 680-688
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- Vernon K. Sondak MD (1)
- Dennis W. King PhD (2)
- Jonathan S. Zager MD (1)
- Schlomo Schneebaum MD (3)
- Julian Kim MD (4)
- Stanley P. L. Leong MD (5)
- Mark B. Faries MD (6)
- Bruce J. Averbook MD (7)
- Steve R. Martinez MD (8)
- Christopher A. Puleo PA-C (1)
- Jane L. Messina MD (1)
- Lori Christman PhD (2)
- Anne M. Wallace MD (9)
- Author Affiliations
- 1. H. Lee Moffitt Cancer Center, Tampa, FL, USA
- 2. STATKING Clinical Services, Fairfield, OH, USA
- 3. Sourasky Medical Center, Tel Aviv, Israel
- 4. University Hospitals Seidman Cancer Center, Cleveland, OH, USA
- 5. California Pacific Medical Center, San Francisco, CA, USA
- 6. John Wayne Cancer Institute, Santa Monica, CA, USA
- 7. MetroHealth Medical Center/Case Western Reserve University, Cleveland, OH, USA
- 8. UC Davis Cancer Center, Sacramento, CA, USA
- 9. San Diego Moores Center Institute, University of California, La Jolla, CA, USA