Castle Biosciences’ DecisionDx-Melanoma Test Shown to be a Significant Predictor of Distant Metastasis in Elderly Patients with Melanoma

“We know that there is a decline in the rate of sentinel lymph node positivity with increasing age, which in turn reflects a greater need for accurate prognostic tools like DecisionDx-Melanoma,” commented Jonathan S. Zager, M.D., FACS, lead study author and Professor of Surgery in the Cutaneous Oncology and Sarcoma Departments at the Moffitt Cancer Center. “These study results confirm that the GEP test is a useful tool for accurately determining metastatic and mortality risk estimates in melanoma patients—including the older patients for whom the decision to perform a sentinel lymph node biopsy may be impacted by increased comorbidities, surgical risk, and shorter life expectancy.”

Performance in Elderly Patients with Melanoma:

In the study, “Melanoma Risk Prediction in Elderly Melanoma Patients with a 31-Gene Expression Profile Test” (poster PF304), 163 patients ≥70 years old were identified from a larger cohort of 521 patients under an IRB-approved multicenter protocol. Older patients with melanoma have high mortality, are more likely to be associated with high-risk features of melanoma, and may receive only limited prognostic value from traditional staging factors such as sentinel lymph node biopsy (SLNB). The DecisionDx-Melanoma test was performed to determine metastatic risk molecular class for each case, with a Class 1 result indicating low risk and Class 2 result indicating high risk. GEP results were analyzed along with SLNB status for the 113 patients who received both. Primary endpoints were distant metastasis-free survival (DMFS), defined as time to any metastatic event beyond the regional nodal basin, and melanoma-specific survival (MSS), defined as time from diagnosis to death due to melanoma.

Summary of Study Results:

• In this elderly patient cohort DecisionDx-Melanoma was a significant predictor of DMFS (p<0.0001 by Cox univariate analysis; p=0.03 by multivariate analysis);
• Results achieved in the multicenter performance study confirm the prognostic accuracy of the DecisionDx-Melanoma test with 5-year DMFS rates of 92% for Class 1 (low risk) and 53% for Class 2 (high risk) patients (p<0.0001). MSS 5-year rates were 98% for Class 1 and 75% for Class 2 (p=0.0003);
• Cox multivariate analysis confirms that the DecisionDx-Melanoma test offers prognostic information that is independent from and adds to conventional staging. The combined GEP/SLN 5-year DMFS rate was 91% for patients who were both SLN negative and Class 1 (compared to 78% for SLN alone) and 40% for those who were SLN positive and Class 2 (compared to 51% for SLN alone; see table below).

Analysis of DMFS and MSS for combined DecisionDx-Melanoma and SLN predicted outcomes in the elderly cohort:

“These data add to the robust support from multiple independent studies showing that DecisionDx-Melanoma is a clinically important tool that can accurately identify a patient’s individual risk of metastasis,” commented Federico A. Monzon, M.D., FCAP, Chief Medical Officer of Castle Biosciences. “Use of the DecisionDx-Melanoma test can complement traditional staging tools to better identify patients at high risk for distant metastasis, enabling implementation of management plans that are consistent with their individual risk.”

Independent, Retrospective Study of Clinical Impact:

Also at the meeting, a study titled, “Impact of Genetic Expression Profile on Decision-Making in Clinically Node Negative Melanoma Patients after Surgical Staging” (poster PF307), was presented by researchers from Oregon Health and Science University. The study evaluated the management of patients who received the DecisionDx-Melanoma test as part of their care following a diagnosis of cutaneous melanoma.

Standard of care recommendations for Stage I or IIA melanoma do not include laboratory testing, frequent exams, or imaging, though the majority of people who die each year from melanoma are diagnosed with early-stage disease. Based on the accurate prognosis of DecisionDx-Melanoma in prospective and retrospective validation studies, the authors included the test in the risk assessment of 119 patients treated between September 2015 and August 2016. In a retrospective analysis of 91 patients in the group who also had a sentinel lymph node biopsy performed, the authors identified patients who were managed with 1) follow-up with dermatology alone, 2) follow-up with surgery alone, 3) follow-up with surgery with recommendation for adjuvant trial, or 4) follow-up with medical oncology and surgery.

Key Findings of the Study:

• 56% (30 of 53) of Class 1 patients were followed by dermatology alone, compared to 0% of Class 2 patients;
• 66% (25 of 38) of Class 2 patients were followed by surgical or medical oncology with recommendation for an adjuvant trial. In comparison, only 19% (10 of 53) of Class 1 patients were followed with this regimen;
• Within pathologic Stage I or Stage II groups, DecisionDx-Melanoma results significantly impacted the management of melanoma patients (p<0.05).

Independent, Prospective, Multicenter Study of Clinical Experience:

A prospective analysis of the DecisionDx-Melanoma test titled, “Combined Experience of Two Tertiary Referral Centers with MelanomaDx GEP Testing” (poster PT286) was presented by researchers at Fox Chase Cancer Center and Thomas Jefferson University Hospital in Philadelphia, PA. Outcomes for 95 patients with Stage I, II or III cutaneous melanoma who received the DecisionDx-Melanoma test in combination with standard staging factors were reported. With a median follow-up time of 11 months, 83 patients had no evidence of disease, seven were alive with disease, and four died of disease.

Key Findings of the Study:

• Recurrences were observed in 4.9% (n=2) of Class 1 patients compared to 24.1% (n=13) of Class 2 patients;
• Of the Class 2 patients who had a recurrence, 77% (10 of 13) had a distant metastasis;
• While Class 2 outcomes were associated with higher rates of ulceration, mitotic activity and positive SLNB, they also had higher rates of first time recurrence and distant metastasis compared to current staging factors.

Two additional studies related to the GEP test were presented at the meeting:

• “Application of Gene Expression Profiling in the Management of Cutaneous Melanoma” by Dr. Xin Huang and colleagues (poster PF307)
• “Utility of Gene Expression Profiling in Determining Necessity of Sentinel Node Biopsy in Melanoma” by Dr. Jennifer K. Keller and colleagues (poster PF319)

About DecisionDx-Melanoma

The DecisionDx-Melanoma test uses tumor biology to provide a prediction of individual risk of melanoma recurrence beyond traditional factors. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in three multi-center studies that have included 690 patients and have demonstrated consistent results. Performance has also been confirmed in two independent, prospective studies including 415 patients. The consistent, high performance and accuracy demonstrated in these studies, which combined have included over 1000 patients, provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. Clinical impact has been demonstrated in a multi-center study showing that test results add additional patient-specific prognostic information to complement traditional staging tools. More information about the test and disease can be found at www.SkinMelanoma.com.

About Castle Biosciences

Castle Biosciences is a molecular diagnostics company dedicated to helping patients and their physicians make the best possible treatment and follow-up care decisions based on the individual molecular signature of their tumor. The Company currently offers tests for patients with cutaneous melanoma (DecisionDx^®-Melanoma; www.SkinMelanoma.com) and uveal melanoma (DecisionDx^®-UM and DecisionDx^®-PRAME; www.MyUvealMelanoma.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-Melanoma, DecisionDx-UM and DecisionDx-PRAME are the trademarks of Castle Biosciences, Inc. Any other trademarks are the property of their respective owners.