Castle Biosciences, Inc., a provider of molecular diagnostics to improve cancer treatment, today announced updated study results with its noninvasive gene expression profile (GEP) test, demonstrating that the assay was able to accurately identify high risk disease in patients with tumors of intermediate thickness (T2/T3), independent of sentinel lymph node biopsy (SLNB) status and ulceration. The data are being presented today at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) during the Melanoma/Skin Cancers Poster Session by David H. Lawson, M.D., Professor of Hematology and Medical Oncology, Winship Cancer Institute, Emory University.
The study, titled “Continued evaluation of a 31-gene expression profile test (GEP) for prediction of distant metastasis (DM) in cutaneous melanoma (CM)” (abstract ID #9066), included results with the GEP test, DecisionDx™-Melanoma, from a total of 555 patients, 270 of whom had T2 or T3 tumors (1.0-4.0 mm thick.)
“In the landmark Multicenter Selective Lymphadenectomy Trial (MSLT-I), up to two-thirds of melanoma patients with tumors of intermediate thickness who metastasized and died from their disease presented with no evidence of nodal metastasis at the time of diagnosis. This important finding confirmed that melanoma is capable of spreading through non-lymphatic mechanisms, and confirmed the importance of tumor (T) factors in predicting risk of distant metastases,” commented Emory’s Dr. Lawson. “The results of this study verify findings from the earlier studies showing that the GEP may be an important addition to currently available staging factors.”
Three consecutive prospectively planned, multicenter clinical validation studies using archival tissue enrolled 555 patients with cutaneous melanoma, 270 of whom had a primary melanoma tumor between 1.0 and 4.0 mm (T2/T3). As expected, the majority of these patients (n=221) were node-negative as assessed pathologically. All patients underwent the DecisionDx-Melanoma gene expression profile test, measuring the activity of 31 genes known to be most associated with progression in this cancer. Based on the tumor’s gene expression levels, each patient’s tumor was classified as either Class 1 “low risk” or Class 2 “high risk.” Primary study endpoints were recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). Consistent with the first two clinical validation studies1,2, the combined results showed that DecisionDx-Melanoma improved the identification of patients at high risk for metastasis and death, independent of sentinel lymph node biopsy status and ulceration.
Summary of Results:
Analysis of DMFS and OS for combination of GEP class and SLNB status results for predicted outcomes in patients with T2/T3 tumors
|n||# of events||5-yr DMFS|
|Class 1/SLN-||53||4 (8%)||94%|
|Class 1/SLN+||29||5 (17%)||79%|
|Class 2/SLN-||84||31 (37%)||63%|
|Class 2/SLN+||55||21 (38%)||62%|
|n||# of events||5-yr OS|
|Class 1/SLN-||53||4 (8%)||94%|
|Class 1/SLN+||28||6 (21%)||76%|
|Class 2/SLN-||83||26 (31%)||67%|
|Class 2/SLN+||52||20 (38%)||60%|
Multivariate analysis of DMFS and OS for GEP class, SLNB status and ulceration status results for predicted outcomes in patients with T2/T3 tumors
|95% Confidence Interval||p-value|
|GEP Class 2||3.8||1.7-8.6||0.001|
|GEP Class 2||3.4||1.6-7.4||0.002|
“Consistent with the results from the first two clinical validation studies, these combined results show that the GEP test identified more than 80 percent of those patients who were at risk of disease progression or death. Importantly, this was true for both the overall group of T2/T3 patients as well as the subgroup who were lymph node-negative and thus often considered at lower risk for metastasis,” said Derek Maetzold, President and CEO of Castle Biosciences. “Not only does the DecisionDx-Melanoma test accurately identify these high risk patients that are missed by today’s staging system, but it also identifies patients who are at very low risk of metastasis with a Class 1 designation. These data provide further validation that DecisionDx-Melanoma is a clinically important tool to identify tumors of intermediate thickness that are at high risk of metastasizing.”
To date, the DecisionDx-Melanoma test has analyzed archived tumor samples from more than 600 melanoma patients in prospectively designed archival tissue studies. More information about the test and disease can be found at www.skinmelanoma.com.
Cutaneous melanoma is diagnosed in approximately 76,000 people in the U.S. each year, according to the American Cancer Society. Seventy-five percent are diagnosed as Stage I or II, meaning there is no evidence of the melanoma spreading beyond the primary tumor. It is not the most prevalent form of skin cancer, but it is the most aggressive. Unlike other more common skin malignancies such as basal cell and squamous cell carcinomas, melanoma often spreads to other parts of the body, either via the lymphatic or blood system, resulting in cancers of distant organs including the brain or lungs. So, while it represents just 4% of skin cancers, melanoma accounts for about 80% of skin cancer-related deaths.
About Castle Biosciences
Castle Biosciences is a molecular diagnostics company dedicated to helping patients and their physicians make the best possible decisions about their treatment and follow-up care based on the individual molecular signature of their tumor. The Company currently offers tests for patients with uveal melanoma (DecisionDx™-UM), cutaneous melanoma (DecisionDx™-Melanoma) and esophageal cancer (DecisionDx™-EC), among others. Castle Biosciences is based in Friendswood, TX (Houston), and has laboratory operations in Phoenix, AZ. More information can be found at www.castlebiosciences.com.
DecisionDx™-UM, DecisionDx™-Melanoma and DecisionDx™-EC are the trademarks of Castle Biosciences, Inc. Any other trademarks are the property of their respective owners.
1Gerami, et al. Development of a Prognostic Genetic Signature to Predict the Metastatic Risk Associated with Cutaneous Melanoma. Clin Cancer Res, 2015 21; 175.
2 Gerami, et al. Gene Expression Profiling for Molecular Staging of Cutaneous Melanoma in Patients Undergoing Sentinel Lymph Node Biopsy. J Am Acad Dermatol. 2015;72(5):780-785.