Results confirm accuracy of DecisionDx-Melanoma to identify recurrence risk
A second independent, prospective study confirms test accuracy
Chicago, IL—June 6, 2016—Castle Biosciences, Inc., a provider of molecular diagnostics to improve cancer treatment decisions, today announced the results from a study evaluating the performance of its gene expression profile (GEP) test, DecisionDx®-Melanoma, in 334 new melanoma patients. The data confirmed the positive results from two previously published multicenter clinical validation studies demonstrating the test’s ability to identify patients’ risk of melanoma recurrence in the 5 years following diagnosis. The data were presented in a poster session at the 2016 American Society of Clinical Oncology Annual Meeting in Chicago, IL. A second, independent, prospective study of DecisionDx-Melanoma was also presented further confirming the results of the three prior multicenter studies.
Expanded Multicenter Performance Study
In a study titled “Performance of a 31-Gene Expression Profile in a Previously Unreported Cohort of 334 Cutaneous Melanoma Patients” (Abstract # 9581), 334 cutaneous melanoma tumors from 12 centers in the U.S. were analyzed using the DecisionDx-Melanoma test. Tumors were classified as either low-risk Class 1 or high-risk Class 2. The test’s prognostic results were compared to actual clinical outcomes over a 5-year period, as well as traditional methods for disease staging and prognosis including sentinel lymph node (SLN) biopsy, ulceration, Breslow thickness and mitotic rate. Study endpoints included recurrence-free survival (RFS), defined as time to either a regional or distant metastatic event; distant metastasis-free survival (DMFS), defined as time to any metastatic event beyond the regional node; and melanoma-specific survival (MSS), defined as time from diagnosis to death documented as specifically resulting from melanoma. A summary of the results is below:
|5-year rate||# of events||5-year rate||# of events||5-year rate||# of events|
|Class 1 (n=181)||86%||29||91%||19||98%||5|
|Class 2 (n=153)||51%||69||60%||54||75%||31|
The study also highlighted the GEP test’s ability to predict which patients are not likely to recur (Negative Predictive Value, or NPV) when used by itself, and in combination with other standard prognostic techniques such as SLN biopsy. While both the DecisionDx-Melanoma test and SLN biopsy were shown to have strong sensitivity to detect patients at risk of metastasis, a combination of the two was the most effective. Results include:
|MSS||SLN Status||GEP Class||SLN + GEP|
|Sensitivity||67% (49-81%)||86% (71-95%)||94% (81-99%)|
|Specificity||72% (66-77%)||59% (53-65%)||48% (42-54%)|
|PPV||22% (15-31%)||20% (14-28%)||18% (13-24%)|
|NPV||95% (91-97%)||97 (94-99%)||99% (95-100%)|
|95% confidence interval shown in parentheses|
Study authors also combined previously studied populations, reviewing the total of 514 patient cases from validation and performance studies of the GEP test to date. Results from the Stage I/II and Stage III patients are shown below:
|MSS||Stage I/II (n=356)||Stage III (n=158)|
|Sensitivity||80% (52-96%)||87% (70-96%)|
|Specificity||65% (60-70%)||32% (24-41%)|
|PPV||9% (5-15%)||24% (16-33%)|
|NPV||99% (96-100%)||91% (79-98%)|
|95% confidence interval shown in parentheses|
“These study results confirm the prognostic accuracy of this GEP test, demonstrating its ability to provide prognostic information that is independent of and additive to conventional staging,” commented Jonathan S. Zager, MD, FACS, lead study author and Professor of Surgery in the Cutaneous Oncology and Sarcoma Departments at the Moffitt Cancer Center. “For melanoma-specific survival, combining this GEP test with SLN status improves sensitivity to 94% and Negative Predictive Value to 99% over SLN status or the GEP test alone – providing support for low-risk management/surveillance plans for Class 1 patients. For Class 2 patients, increased surveillance per guidelines for high-risk patients appears to be warranted.”
“We are extremely pleased with the continued strong performance of our GEP test,” commented Federico A. Monzon, M.D., FCAP, Chief Medical Officer of Castle Biosciences. “The test, when used with standard melanoma staging tools, provides the most accurate prognostic information from which to plan follow-up care. In addition to improving patient care, the GEP test offers the opportunity to improve clinical trial design to advance adjuvant treatment in patients who have a Class 2, high-risk test result.”
Second, Independent, Prospective Study Also Presented
Also at the meeting, a study titled “Prospective Validation of Gene Expression Profiling in Primary Cutaneous Melanoma” (Abstract #9565), was presented by Eddy C. Hsueh, M.D., Professor and Director, Division of Surgical Oncology, St. Louis University Hospital. This study evaluated 159 prospectively enrolled melanoma patients undergoing SLN biopsy and successful testing with the DecisionDx-Melanoma GEP test. The data show that GEP classification is significantly associated with early recurrence in patients diagnosed with melanoma. With a median follow-up time of 18 months, the study found a Negative Predictive Value of 98% for disease-free survival. To date, all Stage III patients with a Class 1 result are recurrence free. The DecisionDx-Melanoma test correctly identified 16 of 18 patients who had recurrence events as high-risk (Class 2). Overall the high-risk Class 2 group had a 38% recurrence rate. Patients who were both high-risk Class 2 and Stage III had a 77% recurrence rate compared to 43% with Stage III status alone.
“An important milestone in test development is demonstrated consistency in prospective studies,” added Derek Maetzold, President and CEO of Castle Biosciences. “This prospective study represents the second such DecisionDx-Melanoma study presented in the last six weeks, and provides further independent confirmation for the consistent results seen in Castle Biosciences’ sponsored multicenter studies.”
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; www.MyUvealMelanoma.com) and cutaneous melanoma (DecisionDx®-Melanoma; www.SkinMelanoma.com), with development programs in other underserved cancers. 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 and DecisionDx-Melanoma are the trademarks of Castle Biosciences, Inc. Any other trademarks are the property of their respective owners.