X. Wang¹, L Mao², Y. Kong², Z. Chi², X. Sheng², C. Cui², B. Lian², X. Yan², L. Si², J Guo²

¹Department of Renal Cancer and Melanoma, China Peking University Cancer Hospital & Institute, Beijing.

²China Peking University Cancer Hospital & Institute, Beijing. 

Objective: BRAF/NRAS mutations are predictors of poor prognosis in melanoma. High-dose interferon (HDI)is the only drug approved by FDA as adjuvant therapy in high risk resected melanomas. However,efficacy of HDI in high-risk melanomas harboring BRAF/NRAS mutations has not been evaluated systemically. This study aimed to clarify whether there is beneficial effect of HDI in these patients. Method: Melanomapatients, after primary lesion or regional metastasis lymphonodus resection, withBRAF mutation (Exon 15) or NRAS mutation (Exon 2) in melanoma of high risk (Stage IIB to Stage IIIC) were enrolled in this study. Patients were randomized(ratio of 2:1) into 1-year adjuvant HDI therapy group and observation group. The endpoint was disease-free survival (DFS). The median follow-up is 36.5 months till Dec. 2014. Somatic mutations were detected by DNA sequencing. All the statistical analyses were performed using SPSS 16.0 software. Result:165 patients were enrolled into the study with 110 patients in HDI group. In 148 eligible patients, proportionof stage IIB/IIC and III disease were 56.8% and 43.2%, respectively.53.4% patients were acral melanomas. Primary ulceration was found in 47.3% lesions. Of the 148 eligible patients, 114cases harbored BRAF mutation, and34 cases with NRAS mutations. At the end of follow-up, 54.1% patients had metastatic or local recurrence. The overall median DFS was 19.0 months. DFS in HDI group was significantly longer than observation group (21.0months vs. 10.0 months, P=0.000).DFS of HDI vs. observation group were 21.0 vs. 10.0 months (P=0.000) inBRAF-mutated patients. These significantly improvement of DFS for HDI adjuvanttherapy also could be found in Non-CSD/CSD and stage III subgroups in BRAF-mutated patients. NRAS-mutated patients did not get significantly benefit from HDI therapy (DFS:24.0 months vs. 20.0 months, P=0.158). Conclusion: Inthe BRAF-mutated high-risk melanoma, HDI may provide beneficial effect in the resected patients. However, more powerful adjuvant therapy should be explored for NRAS-mutated melanoma patients.

KeyWords:Melanoma