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

Abstract

BackgroundA 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.MethodsThree-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).ResultsMedian 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.ConclusionsInterim 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 registrationClinicalTrials.gov, NCT02355574 and NCT02355587 Electronic supplementary materialThe online version of this article (10.1186/s13045-017-0520-1) contains supplementary material, which is available to authorized users.

Melanoma subtypes: genomic profiles, prognostic molecular markers and therapeutic possibilities

“…The test assesses the expression of three control genes, four genes with proven prognostic utility for UMs [31] and 24 genes previously reported to be differentially expressed in metastatic compared to primary tumours [32][33][34][35][36][37][38]. The performance of this test has been evaluated in several retrospective [30,39,40] as well as prospective validation studies [41,42] and has been shown to enhance current prognostic accuracy in particular through identifying clinically and pathologically sentinel lymph node (SLN)-negative patients with high-risk of metastases. However, although there is great promise in reproducibility and clinical validity, the clinical utility for the 31-GEP test on clinical decision-making is still incompletely defined, and will require evidence from further large-scale prospective multi-institutional registry studies before it can be considered for inclusion in any national or professional association guideline recommendations.…”

Early outcome of a 31‐gene expression profile test in 86 AJCC stage IB‐II melanoma patients. A prospective multicentre cohort study

“…This test has been validated in several historical cohorts showing that its prognostic ability is independent from the clinical and pathological features of the tumour. [15][16][17][18][19][20][21][22][23][24] However, this test has never before been evaluated in a prospective multicentre cohort.…”

Identification of risk in cutaneous melanoma patients: Prognostic and predictive markers

“…The difference in MSS between patients with class 1 and class 2 tumors, having stage I to IIA disease, was significant (HR, 6.13; 95% CI, 1.07‐35.24; P = 0.04). The class 2 association with high‐risk disease has been further validated in both a single‐center prospective study that reported a 5‐year RFS rate of 68.7% for class 2 patients, and a multicenter prospective analysis that reported class 2 RFS rates of 77% in a cohort 1.5 years median follow up …”

“…Genes included in the 31‐GEP were distilled from a comparative review of multimarker studies performed between 2000 and 2011, from which over 150 genes associated with recurrence were identified . The test includes three control genes and 28 prognostic genes that have been validated in three multicenter retrospective cohorts, two prospective studies, and an analytic analysis that reported robust reproducibility of the test (98% technical success rate in 8244 clinically tested specimens) . Unlike the tests described above, the 31‐GEP uses radial basis machine (RBM) pattern recognition modeling to compare the GEP of a test sample to a training set containing 164 melanoma tumors with known outcomes.…”

“…In a series of additional retrospective and prospective studies, the 31‐GEP has consistently segregated risk for patients with stage I, II or III tumors . A recent publication analyzed the accuracy of the test in 690 early stage melanoma patients.…”