The FDA has approved the radioactive diagnostic imaging agent Lymphoseek (technetium 99m tilmanocept) Injection to guide sentinel lymph node biopsy in patients with cancer of the head and neck.
The approval is based the phase III NEO3-06 clinical trial in which 83 patients with squamous cell carcinoma of the lip, oral cavity, and skin were injected with Lymphoseek. Suspected lymph nodes identified by Lymphoseek and those based on location and surgical practice were removed for pathological analysis. It was demonstrated that sentinel lymph node biopsy guided by Lymphoseek accurately determined if disease had spread through the lymphatic system.
“For some patients with head and neck cancer, removal and pathological examination of lymph nodes draining a primary tumor is an important diagnostic evaluation,” Libero Marzella, MD, PhD, director of the Division of Medical Imaging Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. “To use Lymphoseek, doctors inject the drug into the tumor area and later, using a handheld radiation detector, find the sentinel lymph nodes that have taken up Lymphoseek’s radioactivity.”
In the NEO3-06 trial, lymph node dissection revealed that 39 patients in the trial had pathologically positive lymph nodes. The Lymphoseek Injection correctly identified 38 of the 39 patients with positive lymph notes, representing a false negative rate of 2.56% (P= 0.0205).
Among the 39 patients with positive nodes, standard multiple level nodal dissection led to the removal of an average of 38 lymph nodes per patient. However, the utilization of Lymphoseek in the trial indicated the removal of only 4 lymph nodes on average per patient. This represents a significant reduction in potential morbidity for patients with head and neck cancer who undergo sentinel lymph node biopsy. No differences were reported in the accuracy of Lymphoseek when surgery was performed the same-day or on a subsequent-day following injection.
"Approximately 75% of patients with stage I and II oral cavity head and neck cancer may be substantially overtreated if they are subjected to elective neck dissection, which involves surgical removal of a regional lymph node chain involving 30 to 45 lymph nodes,” Francisco J. Civantos, MD, FCS, University of Miami School of Medicine, said in a statement. “Receptor-targeted radiopharmaceuticals such as Lymphoseek, that are designed to facilitate accurate and reliable diagnostic evaluation of specific sentinel lymph nodes, can help spare patients morbidity that may result from elective neck dissection procedures."
The trial’s secondary endpoints included the determination of sensitivity (97.6%), negative predictive value (97.8%), and overall accuracy (98.8%) relative to the pathology status of non-sentinel lymph nodes.
The safety of Lymphoseek was also evaluated through observation of adverse events, clinical laboratory tests, vital signs, electrocardiograms, and physical examinations. There were 13 serious adverse events in the trial, though none were associated with Lymphoseek. Additionally, there were no deaths reported in the NEO3-06 trial. The most common side effects associated with Lymphoseek are pain and/or injection site irritation(<1%).
The FDA initially approved the injection for patients with breast cancer or melanoma in March 2013. At the time, the FDA stated that Lymphoseek was the first new drug to gain approval specifically for lymph node mapping in more than 30 years.
In December 2013, Navidea announced that it had submitted a supplemental new drug application following a Fast Track designation from the FDA. In February 2014, the FDA granted a Priority Review for Lymphoseek.
In addition to the already approved indications and in head and neck cancer, Navidea is also developing Lymphoseek in prostate cancer, thyroid cancer, lung cancer, and colorectal cancer.