The Efficacy of Anti-PD-1 Agents in Acral and Mucosal Melanoma

被引：237

作者：

Shoushtari, Alexander N. ^{[1
,2
]}

Munhoz, Rodrigo R. ^{[1
]}

Kuk, Deborah ^{[3
]}

Ott, Patrick A. ^{[4
]}

Johnson, Douglas B. ^{[5
]}

Tsai, Katy K. ^{[6
]}

Rapisuwon, Suthee ^{[7
]}

Eroglu, Zeynep ^{[8
]}

Sullivan, Ryan J. ^{[9
]}

Luke, Jason J. ^{[10
]}

Gangadhar, Tara C. ^{[11
]}

Salama, April K. S. ^{[12
]}

Clark, Varina ^{[1
]}

Burias, Clare ^{[1
]}

Puzanov, Igor ^{[5
]}

Atkins, Michael B. ^{[7
]}

Algazi, Alain P. ^{[6
]}

Ribas, Antoni ^{[13
]}

Wolchok, Jedd D. ^{[1
,2
]}

Postow, Michael A. ^{[1
,2
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Melanoma & Immunotherapeut Serv, 300 East 66th St, New York, NY 10065 USA

[2] Weill Cornell Med Coll, New York, NY USA

[3] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA

[4] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA

[5] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, 221 Kirkland Hall, Nashville, TN 37235 USA

[6] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA

[7] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA

[8] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA

[9] Harvard Med Sch, Massachussetts Gen Hosp, Boston, MA USA

[10] Univ Chicago, Ctr Comprehens Canc, Chicago, IL 60637 USA

[11] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[12] Duke Univ, Sch Med, Durham, NC USA

[13] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA

来源：

CANCER | 2016年 / 122卷 / 21期

基金：

美国国家卫生研究院;

关键词：

acral melanoma; anti-programmed cell death receptor 1 (anti-PD-1); immunotherapy; mucosal melanoma; nivolumab; pembrolizumab; CTLA-4; BLOCKADE; PD-1; IPILIMUMAB; NIVOLUMAB; BIOCHEMOTHERAPY; PEMBROLIZUMAB; SAFETY; UVEAL; CHEMOTHERAPY; PROGNOSIS;

D O I：

10.1002/cncr.30259

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND: Therapeutic antibodies against programmed cell death receptor 1 (PD-1) are considered front-line therapy in metastatic melanoma. The efficacy of PD-1 blockade for patients with biologically distinct melanomas arising from acral and mucosal surfaces has not been well described. METHODS: A multi-institutional, retrospective cohort analysis identified adults with advanced acral and mucosal melanoma who received treatment with nivolumab or pembrolizumab as standard clinical practice through expanded access programs or published prospective trials. Objective responses were determined using investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival and overall survival were assessed using the Kaplan-Meier method. RESULTS: Sixty individuals were identified, including 25 (42%) with acral melanoma and 35 (58%) with mucosal melanoma. Fifty-one patients (85%) had received previous therapy, including 77% who had previously received ipilimumab. Forty patients (67%) received pembrolizumab at a dose of 2 mg/kg or 10mg/kg, and 20 (33%) received nivolumab at a doses ranging from 0.3 to 10 mg/kg every 2 to 3 weeks. The objective response rate was 32% (95% confidence interval, 15%-54%) in patients with acral melanoma and 23% (95% confidence interval, 10%-40%) in those with mucosal melanoma. After a median follow-up of 20 months in the acral melanoma group and 10.6 months in the mucosal melanoma group, the median progression-free survival was 4.1 months and 3.9 months, respectively. Only 2 patients (3%) discontinued treatment because of toxicity. CONCLUSIONS: Response rates to PD-1 blockade in patients with acral and mucosal melanomas were comparable to the published rates in patients with cutaneous melanoma and support the routine use of PD-1 blockade in clinical practice. Further investigation is needed to identify the mechanisms of response and resistance to therapy in these subtypes. (C) 2016 American Cancer Society.

引用

页码：3354 / 3362

页数：9

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