Clinical Efficacy: Solid Tumors
Solid Tumors—Breast Cancer and Melanoma
Lymphoseek® allows precise lymph node identification in patients with solid tumors, including breast cancer or melanomaClinical Study Design1-3
- Efficacy of Lymphoseek was demonstrated in two pivotal Phase 3 open-label, multicenter, single-arm, within-subject active-comparator trials of patients with either melanoma or breast cancer
- A total of 332 patients with melanoma or breast cancer and no nodal or metastatic disease were injected with the following lymph node tracers:
- Lymphoseek, which was given 15 minutes to 15 hours before surgery
- Vital Blue Dye (VBD), which was administered prior to surgery
- Primary endpoint: Concordance of Lymphoseek with VBD
- Diagnostic efficacy was determined by the number of histology-confirmed lymph nodes detected by Lymphoseek. Pathology evaluation determined by the observation of:
- Lymphoseek & vital blue dye present
- Only vital blue dye present
- Only Lymphoseek present
- Neither Lymphoseek nor vital blue dye present
- Lymphoscintigraphy—Approximately 91% of patients underwent preoperative lymphoscintigraphy to facilitate intraoperative lymph node identification
- Intraoperative identification of lymph nodes determined by:
- Detection of Lymphoseek using gamma probe
- Visual detection of VBD
- Visual and palpation of lymph nodes by surgeon
Clinical Efficacy Results
|Resected Lymph Nodes and|
Content of Lymphoseek and/or
Vital Blue Dye (VBD)1† (% [95% CI])
|Study One||Study Two|
|Lymphoseek Only Present
|VBD Only Present
† Percentages might not add up to 100% because of rounding. In clinical studies, Lymphoseek was detectable in lymph nodes within 10 minutes and up to 30 hours.1-3
Lymphoseek, on average, was present in 95% of histopathology confirmed lymph nodes1,4
- Frequently more than one node must be detected for diagnostic evaluation5
- No serious hypersensitivity reactions. The most common adverse reactions are injection site irritation and/or pain (<1%)
Lymphoseek, localized approximately 2 lymph nodes per patient1
Solid Tumors—Squamous Cell Carcinoma (SCC) of the Oral Cavity
Lymphoseek® allows precise lymph node identification in patients with solid tumors, including head and neck squamous cell carcinoma (SCC) of the oral cavity.Clinical Study Design1,2
- Efficacy of Lymphoseek was demonstrated in a Phase 3 open-label, multicenter, single-arm, prospective trial of patients with HNSCC of the oral cavity undergoing lymphoscintigraphy, sentinel lymph node biopsy (SLNB), and elective neck dissection (END).
- END is currently the gold standard for assessing spread to the lymph nodes/lymphatic system in head and neck cancer patients.2,4
- A total of 83 patients with intraoral or cutaneous HNSCC, including 20 patients with floor of mouth tumors, completed the procedure. Patients had no nodal (N0) or metastatic disease (M0) by clinical assessment and had tumor stages T1-4a:
- Patients received 50 ug of Lymphoseek with either 0.5 mCi (1 to <15 hours before surgery) or 2.0 mCi (15-30 hours before surgery)
- SLN biopsy was performed up to 30 hours after injection.2
- Primary endpoint: false negative rate (FNR) of SLN detection by Lymphoseek as confirmed by pathology assessment of lymph nodes removed during a required END.
- Lymphoscintigraphy—100% of patients underwent preoperative lymphoscintigraphy to facilitate intraoperative lymph node identification1
- Sentinel lymph node biopsy (SLNB)
- Elective neck dissection (END)
- Pathology evaluation:
- Lymphoseek present
- Local histopathology standard review of all resected lymph nodes (SLN and non-SLN)
- Lymphoseek-identified nodes determined negative for cancer further evaluated by a central pathology laboratory using additional step sectioning and cytokeratin staining
Clinical Efficacy Results
Lymphoseek identified lymph nodes in 97.6% of patients1
- Low false negative rate—Only 2.6% of all patients with pathology-positive lymph nodes were not identified by Lymphoseek.1
- High sensitivity for detection of patients with cancer in lymph nodes: 97.4%2
- High negative predictive value—98% of patients identified as pathology-negative by Lymphoseek were confirmed as true negative by END.2,3
Minimization of shine-through
- Shine-through—a phenomenon in which radioactivity from the primary tumor site obscures relevant radioactive SNLs—has historically caused difficulties for both preoperative lymphoscintigraphy and intraoperative lymphatic mapping.4
- In a subset of 20 patients with floor of mouth tumors—often a more challenging group of patients with lower rates of SLN identification and higher false negative rates—Lymphoseek identified at least 1 SLN in 100% of patients and facilitated accurate assessment in all patients for a negative predictive value of 100%.2
- It is believed that the rapid movement of Lymphoseek from the primary injection site may minimize the shine-through effect.2
Lymphoseek is a radioactive diagnostic agent indicated with or without scintigraphic imaging for:
- Lymphatic mapping using a handheld gamma counter to locate lymph nodes draining a primary tumor site in patients with solid tumors for which this procedure is a component of intraoperative management.
- Guiding sentinel lymph node biopsy using a handheld gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity, breast cancer or melanoma.
In clinical trials with Lymphoseek, no serious hypersensitivity reactions were reported, however Lymphoseek may pose a risk of such reactions due to its chemical similarity to dextran. Serious hypersensitivity reactions have been associated with dextran and modified forms of dextran (such as iron dextran drugs).
Prior to the administration of Lymphoseek, patients should be asked about previous hypersensitivity reactions to drugs, in particular dextran and modified forms of dextran. Resuscitation equipment and trained personnel should be available at the time of Lymphoseek administration, and patients observed for signs or symptoms of hypersensitivity following injection.
Any radiation-emitting product may increase the risk for cancer. Adhere to dose recommendations and ensure safe handling to minimize the risk for excessive radiation exposure to patients or health care workers.
In clinical trials, no patients experienced serious adverse reactions and the most common adverse reactions were injection site irritation and/or pain (<1%).
Please see full Prescribing Information.
To report suspected adverse reactions, contact Navidea Biopharmaceuticals, Inc. at 1-800-476-5270 or FDA at 1 800-FDA-1088 or www.fda.gov/medwatch.