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Multiple gene mutations may predict recurrence in malignant melanoma

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NEW YORK — Patients with primary malignant melanoma are at a higher risk for tumor recurrence if they have mutations in two or more cancer-related genes, according to study results presented at HemOnc Today Melanoma and Cutaneous Malignancies.

Advanced-stage or recurrent malignant melanoma can be difficult to treat; however, molecular profiling has led to the development of novel treatments — including BRAF, MEK, PD-1 and CTLA-4 inhibitors — and has provided valuable prognostic data.

Francis Si Wai Zih, MD, MSc, FACS, FRCSC, a fellow in the department of surgical oncology at Fox Chase Cancer Center, and colleagues used next-generation sequencing to analyze tissue samples of 108 patients with malignant melanoma for mutations in targeted regions of 50 cancer-related genes. Researchers evaluated whether molecular profiling could predict clinical outcomes.

The analysis included data from 108 patients (median age at diagnosis, 66 years; range, 24-90; 64% men). Forty-nine patients had recurrent melanoma, 24 patients had distant metastases and 15 patients had in-transit disease.

Median follow-up was 12 months.

Researchers reported median OS of 220 months and median DFS of 35 months. At final follow-up, 49 patients (45.3%) demonstrated no evidence of disease, 35 (32.4%) were alive with disease, 19 (17.5%) had died of malignant melanoma and two (1.8%) had died of other causes.

Researchers identified 170 mutations that affected 35 unique genes. Commonly affected genes included NRAS (n = 35), TP53 (n = 23), BRAF V600 (n = 25) and CDKN2A (n = 14).

Fifteen patients (13.8%) harbored no mutations, 52 patients (48.1%) harbored one mutation, and 41 patients (37.9%) harbored two or more mutations.

Sixty-one patients had primary tumor specimens available for next-generation analysis, and 51 had adequate follow-up data available. Researchers reported median DFS of 18 months in this subgroup, and 12 patients (29%) experienced disease recurrence. Results showed patients with two or more mutations experienced significantly shorter DFS (P = .015).

Zih and colleagues suggested future studies assess the correlation between mutation status and response to adjuvant therapy, as well as compare the mutational patterns between primary tumors and subsequent metastases or recurrence. – by Kristie L. Kahl

Reference: Zih FS, et al. Molecular profiling and clinical outcomes in malignant melanoma: Experience at an NCI-designated cancer center. Presented at: HemOnc Today Melanoma and Cutaneous Malignancies; March 18-19, 2016; New York.

Disclosure: The researchers report no relevant financial disclosures.