Gene expression profile test IDs patients at high risk for melanoma

Chicago - Gene expression profiling with a commercially available test (DecisionDx-Melanoma, Castle Biosciences) provides useful prognostic information for patients with high-risk cutaneous melanoma who undergo sentinel lymph node (SLN) biopsy, and particularly for those found to be node-negative, according to a study presented at the annual meeting of the American Society for Clinical Oncology.

The gene expression profile (GEP) test is a signature of 31 genes - 28 discriminating gene targets and three control genes - that classifies tumors into two groups representing a high and low risk of metastasis (Classes 1 and 2, respectively). A previous validation study demonstrated that it accurately predicted the five-year risk of metastasis for primary cutaneous melanomas.

This second validation study investigated its performance for predicting distant metastasis-free survival (DMFS) and overall survival in a cohort of 217 patients with cutaneous melanoma who underwent SLN biopsy. The study results showed GEP testing provided clinically significant information independent of sentinel node status.

“It is important to point out that the GEP test does not take the place of SLN biopsy. Rather, it is another tool for gaining additional prognostic information about patients,” said lead author David Lawson, M.D., who is professor of hematology and oncology, Emory University, Atlanta.

“SLN biopsy is still the best test we have to predict recurrence in a cutaneous melanoma patient who is clinically node-negative,” he says. “However, my experience as a medical oncologist and the results of the Multicenter Selective Lymphadenectomy Trial show that about two of three patients that eventually develop distance metastases had a negative biopsy.

“The GEP test appears to be helpful for identifying which node-negative patients might be at higher risk and perhaps may also improve prognostication for SLN positive patients. However, the question that remains to be answered is what management recommendations should be made to patients based on the findings of the GEP test.”

Derek Maetzold, president and CEO of Castle Biosciences, tells Dermatology Times, “The data from our second validation cohort showed that the GEP test successfully identified a large group of SLN-negative patients who were at very high risk for developing metastasis. This finding is consistent with our first clinical validation study that primarily contained stage 1 and 2 patients and provides good confirmation that we are achieving the goal we had in developing the test.”

Next: Better accuracy

Better accuracy

“In addition, this study shows the findings of GEP and SLN biopsy are complementary. Combining the two results gave better predictive accuracy than either test alone,” Mr. Maetzold says. “We think the added risk information from the GEP test will allow clinicians to better stratify these patients, enabling identification of those individuals who are SLN-negative that merit referral to an oncologist because their tumor biology puts them at risk for internal disease progression.”

The patients in the study underwent SLN biopsy during the years 2000 to 2008, mostly at major academic centers. There were 159 patients who were SLN-negative; the GEP test categorized 92 of those patients as high risk (Class 2) and 67 as low risk (Class 1). Fifty-eight patients were SLN-positive; the GEP test categorized 49 as Class 2 and 9 as Class 1.

Distant metastasis occurred in 32 SLN-positive patients and 53 SLN-negative patients. With patients categorized by GEP class, distant metastasis occurred in 71 Class 2 patients and 14 Class 1 patients.

The group that was SLN-negative and GEP Class 2 had a five-year distant metastasis free survival (DMFS) rate of 49 percent; the DMFS rate for the SLN-negative/Class 1 group was 86 percent.

“Considering SLN status alone, patients who were SLN-positive had a five-year DMFS of 42 percent. The five-year DMFS was similar in the SLN-negative/Class 2 group but, as expected, better in the SLN-negative/Class 1 group. These data further illustrate that the GEP test was able to provide important stratification in the SLN-negative group,” Mr. Maetzold says.

The differences in outcomes between the Class 1 and Class 2 SLN-positive patients were less dramatic, but the results still pointed to added enhanced discrimination with the GEP test information.

In multivariate analysis, both GEP Class 2 and SLN-positive status were independent predictors of DMFS, but GEP was the more powerful of the two, and it was the only significant predictor of overall survival.

Test development

Development of the GEP test was initiated in 2010 with the aim of identifying a tool that could more accurately predict risk of cutaneous melanoma than the current TNM staging criteria - thus representing a useful addition to TNM staging. The initial validation study analyzed data from 268 patients and showed the GEP test accurately stratified patients into low- and high-risk groups and provided information independent of Breslow’s depth, mitotic index, ulceration status or all of those factors combined.

The assay became commercially available in late 2013. Orders are accepted only from treating clinicians who need to submit a one-page requisition form along with a copy of the pathology report for the original tumor biopsy and the patient’s insurance information. Castle Biosciences coordinates obtaining tissue for testing directly through the dermatopathologist, and results are reported to the treating clinician with a turnaround time of 10 to 14 days.

Castle Biosciences also handles insurance billing, and there is an internal charitable program available for patients who are uninsured or who may not be able to afford any out-of-pocket cost for the test.

Disclosures: Dr. Lawson reports no relevant financial interests.