Study Shows Castle Biosciences’ Noninvasive Skin Melanoma Gene Test Improves Accuracy Of Sentinel Lymph Node Biopsy In Predicting Metastasis

Second Clinical Validation Study Results Published in the Journal of the American Academy of Dermatology

FRIENDSWOOD, Texas--(BUSINESS WIRE)--Castle Biosciences, Inc. today announced the publication of a clinical study showing that its gene expression profile (GEP) test for cutaneous (skin) melanoma improved the prognostic accuracy of sentinel lymph node biopsy (SLNB) in identifying patients at high risk of their cancer spreading. The GEP test was able to identify as high risk a significant number of patients whose sentinel lymph node biopsy results did not indicate any increased risk, but who subsequently developed metastatic disease.

“Gene expression profiling for molecular staging of cutaneous melanoma in patients with sentinel lymph node biopsy”

The paper, “Gene expression profiling for molecular staging of cutaneous melanoma in patients with sentinel lymph node biopsy,” was published this week in the Journal of the American Academy of Dermatology (JAAD). Both the SLNB and the GEP test, DecisionDx-Melanoma, were found to be significant predictors of metastatic risk in a multicenter cohort of 217 patients. The GEP test identified approximately 80% of patients at risk for disease progression. Importantly, combining the two prognostic methods showed that patients predicted to be high risk based on the GEP test alone had similar rates of disease progression whether they were SLNB positive or negative. Further, patients who were SLNB negative and also predicted to be low risk using the GEP test had lower rates of disease progression than the SLNB negative group as a whole.

“We know that a positive sentinel lymph node biopsy result identifies 25 to 35 percent of patients who will die from melanoma. The study data show that combined use of SLNB and the gene expression profile test could identify greater than 80 percent of patients with a specificity similar to SLNB alone, giving physicians and patients actionable information for the management of melanoma,” commented Pedram Gerami, M.D., a study author and Associate Professor of Dermatology, Director of Melanoma Research at the Northwestern Skin Cancer Institute, Northwestern University.

Study Details

Primary tumor tissue from 217 Stage I, II, III, or IV cutaneous melanoma patients with documented sentinel lymph node biopsy (SLNB) results was analyzed using the DecisionDx-Melanoma test under a multicenter, prospectively-planned, archival tissue study protocol. The predictive accuracy of the DecisionDx-Melanoma and SLNB prognostic tools were evaluated individually and in combination to assess primary endpoints of disease-free survival (DFS), distant metastasis free survival (DMFS), and overall survival (OS).

As background, sentinel lymph node biopsy is an invasive prognostic procedure used to stage primary melanoma, and is considered among the best tests for identifying high risk or aggressive disease. Given their risk of disease progression, SLNB positive patients are upstaged for baseline imaging, increased monitoring frequency, clinical trial opportunities, adjuvant therapy, and consideration for a lymphatic completion dissection. SLNB has been shown to identify approximately 30% of patients who will ultimately develop metastatic disease and be at risk of death from melanoma. DecisionDx-Melanoma is a noninvasive test developed to identify high risk disease regardless of other diagnostic tests, such as AJCC stage and SLNB status. Using tissue from the primary melanoma, the DecisionDx-Melanoma test measures the expression of 31 genes and stratifies patients as either low risk Class 1 or high risk Class 2.

Independently, the GEP and SLNB tests were shown to stratify patients according to their risk (univariate analysis using Cox proportional hazards p<0.0001 for GEP for all endpoints, SLNB for DFS and DMFS; SLNB for OS p=0.0099).

Individual Kaplan-Meier 5-year DFS, DMFS, and OS for GEP Class and SLNB Status (Log rank)
	DFS (p-value)	DMFS (p-value)	OS (p-value)
GEP
Class 1: Class 2:	79% 34% p<0.0001	82% 46% p<0.0001	89% 55% p<0.0001
SLNB status
Negative: Positive:	55% 37% p<0.0001	64% 42% p<0.0001	71% 62% p=0.006
DFS = disease or recurrence free survival DMFS = distant metastatic free survival OS = overall survival

Multivariate analysis found GEP Class to be independent of SLNB status for all endpoints (p<0.0001) and SLNB status to be independent of GEP Class for DFS (p=0.008) and DMFS (p=0.001) but not OS (p=0.11).

Combining the GEP and SLNB tests showed improvements in stratifying patients who were SLNB negative. The SLNB negative group as a whole had a DFS of 55%. Using the GEP test to further stratify those patients resulted in identification of a higher risk (Class 2) sub-group of SLNB negative patients who had a DFS of 35%. Likewise, SLNB negative patients who were predicted to be low risk (Class 1) using the GEP had a DFS of 83%.

Combined Kaplan-Meier 5-year DFS, DMFS, and OS for GEP Class and SLNB Status (Log rank)
	DFS (p-value)	DMFS (p-value)	OS (p-value)
Class 1 / SLNB negative	83%	86%	91%
Class 1 / SLNB positive	53%	53%	77%
Class 2 / SLNB negative	35%	49%	55%
Class 2 / SLNB positive	33%	42%	57%
p-value	p<0.0001	p<0.0001	p<0.0001

“Similar to our first clinical validation study, this second validation study shows the ability of the DecisionDx-Melanoma test to accurately identify high risk disease,” said Derek Maetzold, President and CEO of Castle Biosciences. “Patients with a Class 2 GEP result have an elevated risk of developing subsequent disease regardless of SLNB status. The test provides clinicians with a method to accurately identify metastatic risk so that management plans can be matched to the patient’s risk of disease progression.”

DecisionDx-Melanoma has been used to analyze archived tumor samples from more than 600 melanoma patients in prospectively designed archival tissue studies. The initial clinical validation of DecisionDx-Melanoma was published earlier this year in the journal Clinical Cancer Research. More information about the test and disease can be found at www.skinmelanoma.com.

The paper can be accessed at: http://dx.doi.org/10.1016/j.jaad.2015.01.009

About Melanoma

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 and prognostics 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 and cutaneous melanoma, esophageal and brain cancers. More information can be found at www.castlebiosciences.com.