The efficacy of anti-PD-1 agents in acral and mucosal melanoma.
The efficacy of anti-PD-1 agents in acral and mucosal melanoma.
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DOI：
10.1002/cncr.30259
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发表时间：
2016-11-15
期刊：
影响因子：
6.2
通讯作者：
Postow, Michael A.
中科院分区：
文献类型：
--
作者：
Shoushtari, Alexander N.;Munhoz, Rodrigo R.;Kuk, Deborah;Ott, Patrick A.;Johnson, Douglas B.;Tsai, Katy K.;Rapisuwon, Suthee;Eroglu, Zeynep;Sullivan, Ryan J.;Luke, Jason J.;Gangadhar, Tara C.;Salama, April K. S.;Clark, Varina;Burias, Clare;Puzanov, Igor;Atkins, Michael B.;Algazi, Alain P.;Ribas, Antoni;Wolchok, Jedd D.;Postow, Michael A.
关键词：
针对程序性死亡受体1（PD-1）的治疗性抗体被认为是转移性黑色素瘤的一线治疗。PD-1阻滞剂对肢端和粘膜表面生物学上不同的黑色素瘤患者的疗效尚未得到充分描述。一项多机构回顾性队列分析通过扩大使用项目或已发表的前瞻性试验确定了接受纳武利尤单抗或派姆单抗治疗的晚期肢端和粘膜黑色素瘤成人患者作为标准临床实践。采用实体瘤疗效评价标准（RECIST）1.1确定客观缓解。使用Kaplan-Meier方法评估无进展（PFS）和总生存期（OS）。确定了60例患者; 25例（42%）肢端黑色素瘤和35例（58%）粘膜黑色素瘤。51例（85%）患者既往接受过治疗，包括77%既往接受过易普利姆玛治疗。40例患者（67%）接受了2 mg/kg或10 mg/kg的pembrolizumab，20例（33%）接受了1 mg/kg或3 mg/kg的nivolumab，每2-3周一次。肢端黑色素瘤的ORR（95%置信区间，CI）为32%（15-54%），粘膜黑色素瘤为23%（10-40%）。在肢端和粘膜中位随访20个月和10.6个月后，中位PFS分别为4.1个月和3.9个月。只有2名患者（3%）因毒性而停止治疗。肢端和粘膜黑色素瘤患者对PD-1阻滞的缓解率与皮肤黑色素瘤的已发表缓解率相当，支持在临床实践中常规使用PD-1阻滞。需要进一步研究以确定这些亚型对治疗的反应和耐药机制。
Therapeutic antibodies against programmed 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. A multi-institutional retrospective cohort analysis identified adults with advanced acral and mucosal melanoma treated with nivolumab or pembrolizumab as standard clinical practice, via expanded access programs, or published prospective trials. Objective responses were determined utilizing investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Progression-free (PFS) and overall survival (OS) were assessed using Kaplan-Meier methods. 60 individuals were identified; 25 (42%) with acral and 35 (58%) with mucosal melanoma. Fifty-one (85%) patients had received prior therapy, including 77% with prior ipilimumab. Forty patients (67%) received pembrolizumab at 2mg/kg or 10mg/kg and 20 (33%) received nivolumab at 1mg/kg or 3mg/kg every 2–3 weeks. ORR (95% confidence interval, CI) was 32% (15–54%) in acral and 23% (10–40%) in mucosal melanoma. After a median follow up of 20 months in acral and 10.6 months in mucosal, median PFS was 4.1 months and 3.9 months, respectively. Only two patients (3%) discontinued treatment due to toxicity. Response rates to PD-1 blockade in patients with acral and mucosal melanomas were comparable to published rates in 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.
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影响因子：
51.1
作者：
Ribas, Antoni;Puzanov, Igor;Dummer, Reinhard;Schadendorf, Dirk;Hamid, Omid;Robert, Caroline;Hodi, F. Stephen;Schachter, Jacob;Pavlick, Anna C.;Lewis, Karl D.;Cranmer, Lee D.;Blank, Christian U.;O'Day, Steven J.;Ascierto, Paolo A.;Salama, April K. S.;Margolin, Kim A.;Loquai, Carmen;Eigentler, Thomas K.;Gangadhar, Tara C.;Carlino, Matteo S.;Agarwala, Sanjiv S.;Moschos, Stergios J.;Sosman, Jeffrey A.;Goldinger, Simone M.;Shapira-Frommer, Ronnie;Gonzalez, Rene;Kirkwood, John M.;Wolchok, Jedd D.;Eggermont, Alexander;Li, Xiaoyun Nicole;Zhou, Wei;Zernhelt, Adriane M.;Lis, Joy;Ebbinghaus, Scot;Kang, S. Peter;Daud, Adil
通讯作者：
Daud, Adil
影响因子：
3.7
作者：
Bello, Danielle M.;Chou, Joanne F.;Ariyan, Charlotte E.
通讯作者：
Ariyan, Charlotte E.
影响因子：
158.5
作者：
Robert, Caroline;Schachter, Jacob;Ribas, Antoni
通讯作者：
Ribas, Antoni
影响因子：
7.3
作者：
Furney, Simon J.;Turajlic, Samra;Marais, Richard
通讯作者：
Marais, Richard
影响因子：
4.3
作者：
Furney, Simon J.;Turajlic, Samra;Marais, Richard
通讯作者：
Marais, Richard