Clinical characteristics of melanoma patients with non-V600E/K BRAF mutations.

Abstract

e20036 Background: BRAF mutations are found in ~50% of melanoma. V600E/K substitutions are the most common and well-characterized. We analyzed the clinical characteristics of patients with non-V600E/K BRAF mutations. Methods: We identified 38 melanoma patients whose tumor contained a non-V600E/K BRAF mutation and reviewed the clinical characteristics. The sequencing analysis was performed with either pyrosequencing or next generation sequencing assay. Results: 38 patients were identified with non-V600E/K BRAF mutations. Mutations detected in more than 1 patient included V600R (n=14, 37%), K601E (5, 13%), G469E (3, 8%); L597S (3, 7%), D594G (2, 5%); 11 other mutations were identified in single patients. Median age was 57 yrs; 82% were men; 95% were white. The common primary subtypes were nodular (26%), superficial spreading (24%), unknown primary (21%); no one were acral, mucosal or uveal melanomas. Ten (26%) of 27 with known ulceration status had ulceration, and 3 (7%) of 22 with known mitosis status had < 1 mitosis /mm2. The sites of primary melanoma were located mostly in the head/neck and the trunk (63%), extremities (16%) and unknown primary (21%). The stage at diagnosis was I /II (29%), III (40%), IV (18%) and unknown (13%). Among 33 (87%) patients who ultimately developed distant metastases, 23(67%) had metastasis in the soft tissue/nodes, 21 (63%) in the lung, 9 (24%) in the brain, 7 (21%) in the liver, 6 (16%) in the bone, and 5 (15%) in the adrenal gland. Among patients (n=25) with initial stage I-III melanoma who later developed distant metastasis, the median duration between the time of initial diagnosis and distant metastases was 36 months. Among the 32 (84%) of the patients who developed stage IV melanoma, the median survival from the time of stage IV diagnosis was 18 months. Five patients received vemurafenib treatment, and 2 patients (K601E; T599_V600ins2) had stable disease and 2 patients (L597Q; G466E) had disease progression and 1 lost to follow up. Conclusions: Unexpectedly higher proportion of the patients with non-V600E/K mutant-melanoma had unknown primary melanoma and higher mitotic rate. In a small number of patients who received vemurafenib, the clinical response appears to be low.