Toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (NCI 2009) . versus 11/78 (14.1%, 95% CI:7.3%-23.8%) in individuals treated with chemotherapy (p=0.87). No tumor response was observed in UM individuals treated with immunotherapy, versus 4/110 reactions (3.6%, 95% CI:1.0-9.0%) in individuals treated with chemotherapy (p=0.15). The modified overall survival (OS) of MM individuals treated with immunotherapy was longer than that of individuals treated with chemotherapy HR=0.62 (95% CI: 0.43-0.91), p=0.014, with an unadjusted median OS Pronase E of 15.97 months [interquartile range (IQR)=6.89-27.11] and 8.82 months [IQR=5.02-14.92], respectively. The modified OS of UM individuals treated with immunotherapy was not significantly different from that of individuals treated with chemotherapy (HR=0.98, 95% CI: 0.66C1.44) p=0.92, with an unadjusted median OS of 13.38 months [IQR=6.03-29.57] and 11.02 months [IQR=6.13-23.93], respectively. Summary Immunotherapy significantly enhances OS for MM. The prognosis of metastatic UM remains poor. 1. Intro Mucosal melanoma (MM) and uveal melanoma (UM) are rare types of melanoma, related to between 4 and 6.8% of melanoma in Caucasians [1C4]. Mucosal melanomas include melanomas located in the sinonasal and oral cavity (50%), anorectal region (25%), urogenital tract (20%), and conjunctiva [5, 6]. Uveal melanomas include melanomas occurring within the choroid, ciliary body, and iris. The prognosis of MM and UM is considered poorer than that of pores and skin melanomas, since they are often diagnosed at an advanced metastatic stage and have particular medical and genetic characteristics . Despite these features, treatment options proposed in individuals with metastatic MM and UM are the same as those TSPAN14 in individuals with pores and skin melanoma. Chemotherapy is definitely poorly effective in MM and even less in UM with response rates ranging from 0 to 15 % [3, 8C10]. Three immune checkpoint inhibitors have been approved in the treatment of individuals with metastatic cutaneous melanoma: ipilimumab, an anti-CTLA-4 monoclonal antibody (mAb), and nivolumab and pembrolizumab, which are both directed against the programmed cell-death protein 1 (PD1). Recent studies showed that these medicines improve the prognosis of individuals with metastatic cutaneous melanoma. Response rates of 10.9% to 15.2% have been reported with anti-CTLA-4 and of 19% to 52% with anti-PD-1 mAbs [11, 12]. Additionally, these second option molecules improved individuals’ survival, with one- and two-year overall survival rates of 68.4% to 72.9% with anti-PD-1 mAbs and of 43% to 55% with anti-CTLA-4 [13C15]. Since UM and MM are quite uncommon, the effectiveness of anti-CTLA-4 and anti-PD-1 mAbs has not been specifically evaluated in large series of individuals with metastatic MM and UM . Rather low response rates between 5 and 17% have been reported with anti-CTLA-4 in MM, related to median overall survival durations between 6.4 and 9.6 months [17C20]. To the best of our knowledge, only a few studies have assessed the effectiveness of anti-PD1 mAbs in limited series of individuals with MM or UM [21, Pronase E 22]. The aim of the present study was to assess the response rate, and overall and progression-free survival in a large multicenter retrospective series of individuals with metastatic MM and UM treated with anti-CTLA-4 or anti-PD-1 mAbs. To compare these results with those previously acquired using chemotherapy regimens, we also assessed the response rate and survival in a series of individuals who were referred for metastatic MM or UM in the same centers before the authorization of anti-CTLA-4 and anti-PD-1 mAbs and were treated with numerous chemotherapy regimens as first-line treatment. 2. Patients and Methods 2.1. Study Design A multicenter retrospective study was performed in the dermatology departments of 25 general- and university or college- private hospitals in France. Individuals with melanoma were recognized using the French (ADICAP) classification. Individuals with UM and MM were secondarily selected. Inclusion criteria were the following: (i) stage III-C to IV (advanced) mucosal or uveal melanoma, whose analysis was histologically confirmed either on the primary tumor or on a metastasis; (ii) individuals who received at least one infusion of anti-CTLA-4 Pronase E or anti-PD-1 mAbs used Pronase E either as 1st or second collection, between 2008 and 2016; (iii) individuals in the chemotherapy subgroup were treated with at least one cycle of.
Toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4
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