Lymphoseek, a radiolabeled sentinel lymph node (SLN) imaging agent, was first approved by the Food and Drug Administration in March 2013 for use in identifying positive SLNs in patients with breast cancer and melanoma.
Now, Lymphoseek is available for commercial use in the United States for those specific indications. In addition, results from a recent interim analysis of a phase 3 trial (NEO3-06) evaluating Lymphoseek in squamous cell carcinoma of the head and neck revealed that the agent also accurately identified SLNs compared with multiple level nodal dissection surgery, which is the current standard of care for determining the extent of disease spread in head and neck cancer.1
“These interim results are highly encouraging for this patient population who generally face extensive surgery to properly stage their cancer,” said Mark J. Pykett, VMD, PhD, President and CEO of Navidea, the biopharmaceutical company that developed Lymphoseek and pre-planned this recent analysis. “This study is part of Navidea’s strategy to expand Lymphoseek utilization into multiple cancer types and assist physicians in improving the accuracy and extent of cancer diagnosis for their patients.”
Of the 80 patients that enrolled on the NEO3-06 trial, 39 were determined to have pathology-positive lymph nodes. Lymphoseek accurately identified 38 of these 39 patients, resulting in a statistically significant false-negative rate—the rate of occurrence of negative test results in individuals known to have the disease—of 2.56% (P= 0.0205). Since the primary endpoint of this trial was reached, Lymphoseek was proven to be predictive of overall node pathology status. Compared to nodal dissection of patients with cancer-positive lymph nodes where an average of 38 nodes were removed, only four nodes were removed in the patients who were injected with Lymphoseek, which significantly reduced potential morbidity.
For patients with head and neck cancer, this represents a significant evolution of terms of diagnosis and staging of their disease; this will help determine the extent of surgical involvement and will direct how the patient is treated post-surgery.
“In the current standard of care with head and neck tumors, we may systematically remove as many as 60 or more lymph nodes within the neck during a formal dissection procedure, a large number due to the likelihood that patients may have hidden cancer in the lymphatic system,” said Stephen Y. Lai, MD, PhD, FACS, an associate professor in the Department of Head and Neck Surgery at The University of Texas M. D. Anderson Cancer Center. “These combined interim data, along with our initial clinical experience with Lymphoseek, suggest a very high level of accuracy in the identification and mapping of SLNs that may significantly improve the precision and practicality of SLN mapping procedures.”
In fact, the top-line results of this interim analysis has driven the study’s Data Safety Monitoring Committee to recommended the trial be closed early in order for Lymphoseek to be indicated sooner, rather than later, for use in patients with head and neck cancer. However, the researchers expect to complete a full dataset in the coming months and the secondary analyses will be presented at future scientific conferences. The possibility of filing a Supplemental New Drug Application later in the year is also being evaluated.
In the meantime, clinicians are already encouraged by Lymphoseek’s utility, particularly in this patient population that often have to endure invasive diagnostic procedures for their head and neck tumors. “This clinical study is unique in that it compares the performance of Lymphoseek, a next-generation, receptor-targeted synthetic molecule to the pathological ‘gold standard’ multiple level dissection procedure in which a large portion of the head and neck lymph node tissue is removed,” said Frederick Cope, PhD, FACN, Senior Vice President of Pharmaceutical Research and Drug Development at Navidea. “Achieving this degree of statistical significance versus the pathology of a multiple level dissection is testimony to the accuracy of Lymphoseek in identifying clinically significant lymph nodes.”
1) Navidea Biopharmaceuticals, Inc. Navidea Biopharmaceuticals Announces Positive Top-Line Results from Interim Analysis of Lymphoseek® Phase 3 Clinical Trial in Head and Neck Cancer [press release]. April 4, 2013. Retrieved at: http://ir.navidea.com/phoenix.zhtml?c=68527&p=irol-newsArticle&ID=1803302&highlight=