Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Unit 455, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J Immunother Cancer. 2017 Dec 19;5(1):100. doi: 10.1186/s40425-017-0301-y.
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.
免疫疗法，特别是基于免疫检查点抑制剂的疗法，在多种肿瘤类型中显示出了有前景的活性。除了欧洲药品管理局批准的用于骨肉瘤的米伐木肽（MEPACT®）外，肉瘤尚无获批的免疫疗法。
我们分析了在 MD 安德森癌症中心参加 1 期临床试验并接受免疫疗法（检查点抑制剂、疫苗或细胞因子治疗）的晚期肉瘤患者的病历。提取了包括人口统计学、临床病史、毒性和反应等临床参数。
在入组免疫治疗试验的 50 名患者（骨 10 例；软组织 40 例）中，我们发现了 14 种不同亚型的肉瘤。皇家马斯登医院（RMH）预后评分<2（86%）。48 名患者的表现状态（PS）为 0-1（96%）；中位既往治疗次数为 3 次（0-12 次）。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%为联合治疗，以及疫苗（14%）和细胞因子（4%）。中位总生存期（OS）为 13.4 个月（未达到 11.2 个月）。中位无进展生存期（PFS）为 2.4 个月（95%CI=1.9-3.2 个月）。两名肺泡软组织肉瘤（ASPS）患者的最佳反应为部分缓解（PR），11 名患者为疾病稳定（SD）（3 名 GIST，3 名脂肪肉瘤（2 名 DDLS，1 名 WDLS），2 名 ASPS，2 名 leiomyo，1 名 osteo）。3 个月时的 PFS 为 34%（23%，在 50%时），6 个月时为 16%（8%，30%），1 年时为 6%（2%，20%）。2 名患者（4%）出现假性进展后疾病稳定。3/4 级不良事件包括皮疹（10%）、发热（6%）、疲劳（6%）和恶心/呕吐（6%）。
在参加试验的晚期肉瘤患者中，免疫疗法耐受性良好。所有四名 ASPS 患者均从检查点抑制剂治疗中获得临床获益，且这是唯一出现部分缓解的亚型。ASPS 患者有必要进一步评估检查点抑制剂。
