Eggermont, Alexander M.M.

e22088 Background: In recent years, adjuvant therapy trials in stage III melanoma have been successful and trials have started with the inclusion of stage IIB/C patients. However, stage IIA melanoma patients are currently not eligible for adjuvant therapy, even though a large part of all melanoma related deaths occur in this patient group. Therefore, a strong clinical need has emerged for diagnostic tools that can identify high-risk patients who currently have no access to adjuvant therapy. Here, we sought to assess the ability of a recently introduced clinicopathologic gene expression model (CP-GEP) (Bellomo et al., JCO Precis Oncol. 2020: in press) to select stage IIA patients at high risk for disease relapse, upon design of a stage-specific operating point. Methods: We assessed the prognostic performance of the CP-GEP model in all 141 stage IIA patients from a Mayo Clinic cohort of 837 consecutive melanoma patients who had a sentinel lymph node biopsy (SLNb) performed within 90 days of their diagnosis. The CP-GEP model combines Breslow thickness and patient age, with the expression of 8 genes in the primary tumor. Moreover, it stratifies patients according to their risk of relapse: CP-GEP High Risk or CP-GEP Low Risk, based on an operating point that was specifically developed for stage IIA. This stage-specific operating point was selected to fulfill the following criteria: hazard ratio RFS > 2 with a p-value < 0.05, and risk groups of similar size. The main clinical endpoint was five-year relapse free survival (RFS). Results: The CP-GEP High Risk group corresponds to 45% (63/141) of all stage IIA patients and captures 62% (18/29) of the total relapses in this substage. Moreover, CP-GEP High Risk patients relapse more frequently than CP-GEP Low Risk patients (RFS of 56% versus 78%; HR, 2.23; P < 0.05). The prognosis for stage IIA CP-GEP High Risk patients in our cohort is worse than for stage IIC/IIIA patients with reported RFS ranging from 63% to 77%. Conclusions: The CP-GEP model can be optimized by designing a stage-specific operating point, to identify a subset of stage IIA patients with an increased risk for disease relapse, not very different from IIC/IIIA patients. Therefore, stage IIA CP-GEP High Risk patients may be considered for inclusion in adjuvant trials. Independent validation studies are ongoing for the newly developed operating point. [Table: see text]

10068 Background: The identification of early stage melanoma patients at high risk for relapse is still difficult. Roughly 50% of melanoma deaths occur in patients who were initially diagnosed with nonmetastatic melanoma. Therefore, a strong clinical need has emerged for diagnostic tools that can identify melanoma patients at high risk for relapse. Here, we assessed the performance of a recently developed model (Bellomo et al., JCO Precis Oncol. 2020: in press), combining clinicopathologic and gene expression variables (CP-GEP), in identifying melanoma patients that have a high risk for disease relapse. Methods: We assessed the prognostic performance of the CP-GEP model in a cohort of 837 consecutive melanoma patients from Mayo Clinic who had a sentinel lymph node biopsy (SLNb) performed within 90 days of their diagnosis. The CP-GEP model combines Breslow thickness and patient age, with the expression of 8 genes in the primary tumor, to stratify patients according to their risk of relapse: CP-GEP High Risk or CP-GEP Low Risk. The main clinical endpoint of this study was five-year relapse free survival (RFS). Results: Patients were stratified based on SLNb status and CP-GEP classification. 76% of the patients were SLNb negative and had an RFS of 79% versus 52% for SLNb positive patients; HR, 3.21; P < 0.0001. 60% of the patients were identified as CP-GEP High Risk and had an RFS of 62% versus 87% for CP-GEP Low Risk patients; HR, 4.12; P < 0.0001. Within the SLNb negative group (637 patients of which 65% stage I), 51% of patients were classified as CP-GEP High Risk. Here, RFS was 70% for CP-GEP High Risk patients versus 89% for CP-GEP Low Risk patients; HR, 3.61; P < 0.0001. The prognosis of these CP-GEP High Risk patients is similar to stage IIC/IIIA patients with reported RFS ranging from 63% to 77%. This confirms the heterogeneity in prognosis among patients with stage I/II melanoma disease. Conclusions: The CP-GEP model can be successfully used to stratify patients based on their risk for relapse. In particular, it can be used to identify SLNb negative patients with a high risk for disease relapse who may benefit from therapeutic interventions. Independent validation studies are ongoing to validate the CP-GEP model in various patient populations. [Table: see text]