Interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test

Journal of Hematology & Oncology, Sep 2017

A 31-gene expression profile (GEP) test that provides risk classification of cutaneous melanoma (CM) patients has been validated in several retrospective studies. The objective of the reported study was a prospective evaluation of the GEP performance in patients enrolled in two clinical registries. Three-hundred twenty two CM patients enrolled in the EXPAND (NCT02355587) and INTEGRATE (NCT02355574) registries met the criteria of age ≥ 16 years, successful GEP result and ≥1 follow-up visit for inclusion in this interim analysis. Primary endpoints were recurrence-free (RFS), distant metastasis-free (DMFS), and overall survival (OS). Median follow-up was 1.5 years for event-free patients. Median age for subjects was 58 years (range 18–87) and median Breslow thickness was 1.2 mm (range 0.2–12.0). Eighty-eight percent (282/322) of cases had stage I/II disease and 74% (237/322) had a SLN biopsy. Seventy-seven percent (248/322) had class 1 molecular profiles. 1.5-year RFS, DMFS, and OS rates were 97 vs. 77%, 99 vs. 89%, and 99 vs. 92% for class 1 vs. class 2, respectively (p < 0.0001 for each). Multivariate Cox regression showed Breslow thickness, mitotic rate, and GEP class to significantly predict recurrence (p < 0.01), while tumor thickness was the only significant predictor of distant metastasis and overall survival in this interim analysis. Interim analysis of patient outcomes from a combined prospective cohort supports the 31-gene GEP’s ability to stratify early-stage CM patients into two groups with significantly different metastatic risk. RFS outcomes in this real-world cohort are consistent with previously published analyses with retrospective specimens. GEP testing complements current clinicopathologic features and increases identification of high-risk patients. ClinicalTrials.gov, NCT02355574  and NCT02355587

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Interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test

Hsueh et al. Journal of Hematology & Oncology Interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test Eddy C. Hsueh 2 James R. DeBloom 1 Jonathan Lee 0 Jeffrey J. Sussman 6 Kyle R. Covington 5 Brooke Middlebrook 5 Clare Johnson 5 Robert W. Cook 5 Craig L. Slingluff Jr 4 Kelly M. McMasters 3 0 Northside Melanoma and Sarcoma Specialists of Georgia , Atlanta, GA , USA 1 South Carolina Skin Cancer Center , Greenville, SC , USA 2 Dept. of Surgery, St. Louis University , St. Louis, MO , USA 3 Dept. of Surgical Oncology, James Graham Brown Cancer Center, University of Louisville School of Medicine , Louisville, KY , USA 4 Dept. of Surgery and Cancer Center, University of Virginia School of Medicine , Charlottesville, VA , USA 5 Castle Biosciences, Inc. , 820 S. Friendswood Drive Suite 201, Friendswood, TX , USA 6 Dept. of Surgery, University of Cincinnati Cancer Institute , Cincinnati, OH , USA Background: A 31-gene expression profile (GEP) test that provides risk classification of cutaneous melanoma (CM) patients has been validated in several retrospective studies. The objective of the reported study was a prospective evaluation of the GEP performance in patients enrolled in two clinical registries. Methods: Three-hundred twenty two CM patients enrolled in the EXPAND (NCT02355587) and INTEGRATE (NCT02355574) registries met the criteria of age ≥ 16 years, successful GEP result and ≥1 follow-up visit for inclusion in this interim analysis. Primary endpoints were recurrence-free (RFS), distant metastasis-free (DMFS), and overall survival (OS). Results: Median follow-up was 1.5 years for event-free patients. Median age for subjects was 58 years (range 18-87) and median Breslow thickness was 1.2 mm (range 0.2-12.0). Eighty-eight percent (282/322) of cases had stage I/II disease and 74% (237/322) had a SLN biopsy. Seventy-seven percent (248/322) had class 1 molecular profiles. 1.5-year RFS, DMFS, and OS rates were 97 vs. 77%, 99 vs. 89%, and 99 vs. 92% for class 1 vs. class 2, respectively (p < 0.0001 for each). Multivariate Cox regression showed Breslow thickness, mitotic rate, and GEP class to significantly predict recurrence (p < 0.01), while tumor thickness was the only significant predictor of distant metastasis and overall survival in this interim analysis. Conclusions: Interim analysis of patient outcomes from a combined prospective cohort supports the 31-gene GEP's ability to stratify early-stage CM patients into two groups with significantly different metastatic risk. RFS outcomes in this real-world cohort are consistent with previously published analyses with retrospective specimens. GEP testing complements current clinicopathologic features and increases identification of high-risk patients. Trial registration: ClinicalTrials.gov, NCT02355574 and NCT02355587 Gene expression profiling; DecisionDx-Melanoma; Cutaneous melanoma; Metastasis; Prognosis; Staging Background The majority of cutaneous melanoma (CM) patients are diagnosed with early-stage (AJCC stage I or II) disease and are considered to have a favorable prognosis [ 1, 2 ]. However, two-thirds of all melanoma deaths occur in patients initially included in this “low-risk” group, which indicates that metastatic risk is underestimated for a substantial number of early-stage patients [ 1–4 ]. A recent study reporting data from the Surveillance, Epidemiology, and End Results (SEER) program reported that the mortality rate for cutaneous melanoma is increasing faster than the incidence rate, highlighting the need for additional prognostic tools to supplement standard clinicopathologic factors and improve identification of high-risk disease [ 5 ]. More vigilant follow-up for high-risk melanoma patients, including the addition of imaging and increasing clinical assessment frequency, leads to earlier detection of asymptomatic distant metastatic disease, when tumor burden is lower, and when surgical approaches as well as contemporary therapies have greater benefit [ 5–11 ]. Distinguishing those CM patients with high-risk tumor biology from those who are categorized as low risk by TNM staging alone is therefore a clinically important goal. A prognostic gene expression profile (GEP) test (DecisionDx-Melanoma, Castle Biosciences, Inc.) that evaluates 31 gene targets expressed in the primary melanoma tumor to provide a binary classification of low (class 1) or high (class 2) risk of metastasis within 5 years of the initial diagnosis has been previously reported [ 12 ]. The test assesses the expression of three control genes, four genes with proven prognostic utility for uveal melanoma tumors [ 13 ], and 24 gene targets previously reported to be differentially expressed in metastatic compared to primary tumors [ 14–20 ]. Performance of the test has been evaluated in several retrospective validation studies, showing that it accurately prognosticates (...truncated)


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Eddy C. Hsueh, James R. DeBloom, Jonathan Lee, Jeffrey J. Sussman, Kyle R. Covington, Brooke Middlebrook, Clare Johnson, Robert W. Cook, Craig L. Slingluff, Kelly M. McMasters. Interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test, Journal of Hematology & Oncology, 2017, pp. 152,