L. Si¹,  Y. Kong², X.Wang²,  ZH.Chi²,  CL.Cui²,  XN.Sheng²,  LL. Mao², BX. Tang²,  B.Lian²,  XQ.Yan², J Guo²

¹Department of Renal Cancer and Melanoma, China Peking University School of Oncology, Beijing Cancer Hospital, Beijing.

²China Peking University School of Oncology, Beijing Cancer Hospital, Beijing.

Objective:Everolimus, anoral mTOR inhibitor,hasshown minimal activity as a single agent in patients with metastatic melanoma unselected for potential predictive biomarkers (J Clin Oncol 24:463s,2006). However,selection of patients with melanoma harboring mTOR mutations may improve the efficiency of mTOR inhibitor inpatients with melanoma (J Clin Oncol. 2012,30(4):e37-40).This study (NCT01960829) aims to observe the efficacy of mTOR inhibitor inmelanoma patients with mTOR mutations (mut). Method: Ptswith unresectable melanoma whose tumor harbored mutation in mTOR and who had measureable disease by RECIST and failed from systemic treatment (at lease 1) were eligible. Pts received everolimus 10 mg daily continually until disease progression or unacceptable toxicity. Response assessments were performed every 8 weeks. The endpoints were progression-free survival (PFS) and overall survival. Result:Of 396 pt tumors screened, 10.3% had a mTOR mut: 22/207 (10.6%) acral, 15/104 (14.4%) mucosal, 2/28 (7.1%) CSD and 3/57 (5.2%) Non-CSD. Thus far, 8 have been treated, with6 pts currently evaluable for response. Median age: 54yrs (range, 38-65); 3 male/ 5 female; median of prior therapies: 2(range, 1-4). The 6 pts achieved stable diseases. The PFS were 26 weeks+ (Exon 41:G5741C, acralfailed of DTIC, DDP and PTX), 18weeks+ (Exon 41: A5794G, mucosalfailed of TMZ, bevacizumab: BEV, DDP and nab-PTX), 17weeks+ (Exon 41: G1914R, acrafailed of DTIC), 12weeks+ (Exon 46: C6520T, acralfailed of TMZ, carboplatin, BEV, PTXand fotemustine ), 11 weeks+ (Exon 47: C6637T, mucosalfailed of nab-PTX, DDP and TMZ) and 10 weeks+ (Exon 43: C6026T, CSD failedof DTIC,DDP,BEVand PTX) respectively. All the 6 pts had median tumor shrinkage (12%, 10%, 9%, 23%, 1%and 5% respectively). Conclusion: In this pt population, mTOR mut was more frequent in acral and mucosal tumors. While mTOR inhibitor has limited activity in a non-selected melanoma ptpopulation, a substantial proportion of melanomas harboring mTOR mut appear to respond. It may be possible to identify appropriate pts prospectively for treatment with mTOR inhibitors. (Supported by the National Natural Science Foundation of China (81301984), the Beijing Nova Program(2013027) and Novartis Oncology in China) .

Key Words:melanoma