2024 Key Insights: Skin Cancer

As we approach the end of the fall conference season in dermatology, I find myself reflecting on the fact that the conferences that we as practicing dermatologists attend are very often limited to those that match our clinical focus—and, as a result, we may miss important updates that are presented at relevant conferences that fall outside our field of view. Over the past year there have been significant advances in the evidence supporting the use of gene expression profile (GEP) testing to inform decision-making for patients with cutaneous melanoma.^1,2 What is more, there have also been several impactful conference presentations at high-impact meetings outside dermatology where investigators released up-to-date research findings on the specific role of GEP tests to inform sentinel lymph node biopsy (SLNB) decision-making for patients. Given the relevance to dermatologists, who are so often making decisions about which patients to route to surgical oncology and multidisciplinary care, it is worth reviewing these updates as these findings are making their way into journals. The 2 conferences and presentations I am referring to were both delivered by surgical oncologists and are reviewed here.

1: March 2024 Society of Surgical Oncology Annual Meeting

J. Michael Guenther, MD, presented “Prospective Validation of the i31-GEP for Cutaneous Melanoma to Select Patients Who May Consider Forgoing SLNB.”

This oral presentation discussed the updated results of the DECIDE trial (DecisionDx-Melanoma impact on sentinel lymph node biopsy decisions and clinical outcomes; i31-GEP), which is a prospective, multicenter study evaluating 3 aims for patients with T1-T2 cutaneous melanoma: (1) the ability of clinicians to use i31-GEP test result to inform clinical SLNB decision-making, (2) for clinicians and patients who did not use the i31-GEP test to avoid SLNB, do the patients predicted to have a low risk of SLN positivity have an actual low rate of false negative GEP results, and (3) for clinicians and patients who used the i31-GEP test to avoid an SLNB based on low-risk GEP test results, did they experience low rates of disease progression or adverse outcomes. Guenther’s presentation provided a signi cant update to this trial and reported that in 322 patients with T1aT2b cutaneous melanoma, those who received a less than 5% i31SLNB test result and who proceeded to have SLNB performed had a 0% SLN positivity rate. Next, Guenther presented the first clinical outcomes date from the multicenter DECIDE trial and now with 2 years of median follow-up time, there have been no class 1A (low-risk of disease progression) patients who have experienced a recurrence or distant metastasis.

In summary, these data confirm 2 key findings related to DecisionDx-Melanoma: that patients predicted to have a low risk of SLN positivity based on i31-GEP SLNB result had a confirmed low incidence of positive SLN, and that over the course of study to date, there have been no recurrence or metastasis events which includes the approximately 18% of patients who forwent SLNB based on DecisionDx-Melanoma test results.³

2: October 2024 Society for Melanoma Research Congress

Vernon Sondak, MD, presented “Prospective Multicenter Evaluation (MERLIN_001 trial) of a Clinicopathologic and Gene Expression Profile Test to Predict Sentinel Node Status in T1-T3 Cn0 Melanoma.” 

This oral presentation discussed the results of the MERLIN_001 trial (NCT04759781), which is a prospective multicenter registry study designed to validate the MERLIN CP-GEP test. The predefined primary objective was to determine if the low-risk CP-GEP test result could identify patients who could safely forgo an SLNB—being defined as an actual SLN positivity rate of less than 5%. The study evaluated 1686 patients who had the MERLIN test performed experimentally and who subsequently underwent SLNB with the surgeon and patient blinded to the result. 

The primary results from the predefined primary objective failed to be achieved; specifically, the SLN positivity rate in the Merlin low-risk CP-GEP test group was found to be 7.1%. Subsequent analyses in any study with a failed primary end point are to be viewed as exploratory only. However, Sondak did present predefined secondary subanalyses. Specifically, in patients with Editor in Chief, Spring Aaron Farberg, MD Dallas, Texas stage IB the SLN positivity rate in the Merlin low-risk CP-GEP group was 6.4%, and in patients 65 and older, the SLN positivity rate in the low-risk CP-GEP group was 6.2%. In summary, the MERLIN_001 study was designed to evaluate if the CP-GEP test could identify low-risk patients who fall below the established 5% SLN positivity risk threshold; the results showed that the study failed, in that patients in the low-risk CP-GEP test group had a true SLN positivity rate of 7.1%, exceeding the 5% threshold.

Both presentations reviewed here underscore the continued research advances in the clinical utility of GEP tests to inform decisions for patients with cutaneous melanoma. They also highlight key differences in both study design and GEP test performance among clinically available GEP tests for our patients, which is not surprising when we look to the multiple GEP tests used in breast and prostate cancers which also show clinically different performance characteristics.

From a top-line perspective, the results from the prospective, multicenter DECIDE study were positive and consistent with prior studies in that the DecisionDx-Melanoma test was able to both accurately identify patients who have a less than 5% of SLN positivity and who are also unlikely to experience disease progression. While the MERLIN_001 trial included a large number of experimentally tested patients, the study failed to meet its clinical validity end point, and the low-risk CP-GEP patients were not low risk enough to forgo the SLNB procedure. None of the clinicians involved in the MERLIN_001 study used the results to guide management, which further limits the ability to extrapolate clinical utility claims from this study.⁴

I, for one, am looking forward to 2025 and the continued research advances and subsequent publication of the results from both DECIDE and MERLIN_001. As always, stay tuned for more updates.

Aaron S. Farberg, MD, is a double board-certified dermatologist, Mohs surgeon, chief medical officer at Bare Dermatology in Dallas, Texas, and Dermatology Times’ spring 2024 editor in chief.

References
1. Podlipnik S, Martin BJ, Morgan-Linnell SK, et al. The 31-gene expression profile test outperforms AJCC in stratifying risk of recurrence in patients with stage I cutaneous melanoma. Cancers (Basel). 2024;16(2):287. doi:10.3390/cancers16020287
2. Kriza C, Martin B, Bailey CN, Bennett J. Integrating the melanoma 31-gene expression profile test with clinical and pathologic features can provide personalized precision estimates for sentinel lymph node positivity: an independent performance cohort. World J Surg Oncol. 2024;22(1):228. doi:10.1186/s12957-024-03512-4
3. Guenther JM. Prospective validation of the i31-GEP for cutaneous melanoma to select patients who may consider forgoing SLNB. Presented at: 2024 Society of Surgical Oncology Annual Meeting; March 20-23, 2024; Atlanta, GA.
4. Sondak V. Prospective multicenter evaluation (MERLIN_001 trial) of a clinicopathologic and gene expression profile test to predict sentinel node status in T1-T3 cN0 melanoma. Presented at: 2024 Society for Melanoma Research; October 10-13, 2024; New Orleans, LA.