Characteristics and outcomes of patients with advanced sarcoma enrolled in early phase immunotherapy trials.
Characteristics and outcomes of patients with advanced sarcoma enrolled in early phase immunotherapy trials.
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DOI：
10.1186/s40425-017-0301-y
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发表时间：
2017-12-19
影响因子：
10.9
通讯作者：
Subbiah V
中科院分区：
文献类型：
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作者：
Groisberg R;Hong DS;Behrang A;Hess K;Janku F;Piha-Paul S;Naing A;Fu S;Benjamin R;Patel S;Somaiah N;Conley A;Meric-Bernstam F;Subbiah V
免疫疗法，特别是基于免疫检查点抑制剂的免疫疗法，在多种肿瘤类型中显示出有希望的活性。除了欧洲药品管理局批准用于骨肉瘤的米法莫肽（MEPACT®）外，没有批准用于肉瘤的免疫疗法。我们分析了转入MD安德森中心一期临床并接受免疫治疗（检查点抑制剂、疫苗或基于细胞因子的治疗）的晚期肉瘤患者的医疗记录。临床参数包括人口统计学、临床病史、毒性和反应被抽象化。在参加免疫治疗试验的50例患者中（骨10例；软组织40例），我们发现了14种不同亚型的肉瘤。英国皇家马斯登医院（RMH）预后评分<2（86%）。48例（96%）患者表现状态（PS）为0-1；既往治疗中位数为3（0-12）。免疫治疗包括检查点抑制剂（82%:PD1 = 7, PD-L1 = 11, CTLA4 = 22，其他= 1），其中42%为联合用药，以及疫苗（14%）和细胞因子（4%）。中位总生存期（OS）为13.4个月（11.2个月：未达到）。中位无进展生存期（PFS）为2.4个月（95% CI = 1.9-3.2个月）。2例肺泡软组织肉瘤（ASPS）患者的最佳反应是部分缓解（PR）， 11例患者的最佳反应是病情稳定（SD）（3例GIST， 3例脂肪肉瘤（2例DDLS， 1例WDLS）， 2例ASPS， 2例平滑肌，1例骨肉瘤）。3个月时PFS为34%(23%,50%)，6个月时为16%(8%,30%)，1年时为6%（2%,20%）。2例（4%）患者出现假进展，随后病情稳定。3/4级不良事件包括皮疹（10%）、发烧（6%）、疲劳（6%）和恶心/呕吐（6%）。免疫疗法在参与试验的晚期肉瘤患者中耐受性良好。所有4名ASPS患者使用检查点抑制剂均有临床获益，这是唯一出现部分反应的亚型。检查点抑制剂在ASPS中的进一步评估是有必要的。
Immunotherapies, specifically those based on immune checkpoint inhibitors, have shown promising activity in multiple tumor types. Other than mifamurtide (MEPACT®) for osteosarcoma approved by European Medicines Agency, there are no approved immunotherapies for sarcomas. We analyzed medical records of patients with advanced sarcoma who were referred to Phase 1 clinic at MD Anderson and received an immunotherapy (checkpoint inhibitors, vaccines, or cytokine based therapies). Clinical parameters including demographics, clinical history, toxicity, and response were abstracted. Among 50 patients enrolled in immunotherapy trials (Bone 10; Soft-tissue 40) we found 14 different subtypes of sarcomas. Royal Marsden Hospital (RMH) prognostic score was <2 (86%). Performance status (PS) was 0–1 in 48 patients (96%); median number of prior therapies was 3 (0–12). Immunotherapy consisted of checkpoint inhibitors (82%: PD1 = 7, PD-L1 = 11, CTLA4 = 22, other = 1) of which 42% were combinations, as well as vaccines (14%), and cytokines (4%). Median overall survival (OS) was 13.4 months (11.2 months: not reached). Median progression free survival (PFS) was 2.4 months (95% CI = 1.9–3.2 months). Best response was partial response (PR) in 2 patients with alveolar soft part sarcoma (ASPS) and stable disease (SD) in 11 patients (3 GIST, 3 liposarcomas (2 DDLS, 1 WDLS), 2 ASPS, 2 leiomyo, 1 osteo). PFS was 34% (23%, at 50%) at 3 months, 16% (8%, 30%) at 6 months, and 6% (2%, 20%) at 1 year. Pseudo-progression followed by stable disease was observed in 2 patients (4%). Grade 3/4 adverse events included rash (10%), fever (6%), fatigue (6%), and nausea/vomiting (6%). Immunotherapies were well tolerated in advanced sarcoma patients enrolled in trials. All four ASPS patients had clinical benefit with checkpoint inhibitors and this was the only subtype experiencing partial response. Further evaluation of checkpoint inhibitors in ASPS is warranted.
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DOI：
10.1158/1078-0432.ccr-16-3133
发表时间：
2017-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
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作者：
Kato S;Goodman A;Walavalkar V;Barkauskas DA;Sharabi A;Kurzrock R
通讯作者：
Kurzrock R
影响因子：
--
作者：
Groisberg R;Hong DS;Holla V;Janku F;Piha-Paul S;Ravi V;Benjamin R;Kumar Patel S;Somaiah N;Conley A;Ali SM;Schrock AB;Ross JS;Stephens PJ;Miller VA;Sen S;Herzog C;Meric-Bernstam F;Subbiah V
通讯作者：
Subbiah V
影响因子：
6.4
作者：
Fujii, Hiroko;Arakawa, Akiko;Tanioka, Miki
通讯作者：
Tanioka, Miki
DOI：
10.2165/11204910-000000000-00000
发表时间：
2010-06-01
期刊：
Paediatric drugs
影响因子：
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作者：
Frampton, James E
通讯作者：
Frampton, James E
影响因子：
28.2
作者：
Kim ES;Herbst RS;Wistuba II;Lee JJ;Blumenschein GR Jr;Tsao A;Stewart DJ;Hicks ME;Erasmus J Jr;Gupta S;Alden CM;Liu S;Tang X;Khuri FR;Tran HT;Johnson BE;Heymach JV;Mao L;Fossella F;Kies MS;Papadimitrakopoulou V;Davis SE;Lippman SM;Hong WK
通讯作者：
Hong WK