医脉通编译，转载请务必注明出处
2016年6月3-7日，一年一度的美国临床肿瘤学会（American Society of Clinical Oncology，ASCO）年会在芝加哥举办。6月5日上午的消化系统（结直肠）肿瘤口头报告专场上，一项摘要号为3502的NCI9673 II期试验，在难治性转移性肛管鳞状细胞癌（SCCA）患者中给予nivolumab治疗，医脉通整理如下：
肛管鳞状细胞癌（SCCA）的发病率在美国每年持续上升。20%的患者进展为转移性病变，缺少一种共识方法来提供治疗。SCCA很大程度上受HPV-特异性CD8和CD4 T细胞免疫逃避驱动，这会促进SCCA肿瘤形成。Nivolumab（Nivo），一种靶向T细胞PD-1的单克隆抗体，在体外提高免疫介导的T细胞反对HPV-阳性细胞的抗肿瘤活性。这是首项Nivo用于难治性转移性SCCA患者的II期试验。
之前接受过治疗而非免疫治疗的患者符合入组条件。PD-L1表达不是必须条件。HIV+（CD计数＞300/uL）和乙型/丙型肝炎患者符合条件。从而开展一项Simon二阶段的II期试验（Ho：P＜0.05，Ha：P≥0.20）。所有患者按照RECIST标准1.1进行评估。患者接受Nivo（3mg/kg）IV每2周。研究人员收集可选的前治疗和治疗中的组织活检及血浆样本用于免疫标记物和HPV/p16状态。所有关联度分析通过免疫治疗平台团队和核心设备（Immunotherapy Platform team and the Core Facility）在MDACC进行评估。
39例患者通过ETCTN网络被筛查（2015年5月-2015年10月）；37例患者符合要求。中位年龄是56岁（四分位范围[IQR]，51.1-63.6）；男女比例为12:25。事先接受过治疗的中位数是2次（范围1-8）。所有患者对毒性进行评估；33例患者对反应进行评估。中位周期数是6（IQR，3-10）。7例（21%）患者出现部分响应，19例患者（58%）病情稳定；疾病控制率为79%。10例（1例为HIV+）患者仍在研究中（7例患者持续＞6个月[男性]）。中位无进展生存期是4.1个月。常见的不良事件（AE）是乏力，恶心，和皮疹。6例患者出现3级AEs：乏力（n=2），肺炎，皮疹，贫血和高血糖各1例。
目前，对于转移性肛管鳞状细胞癌的治疗没有达成共识。NCI9673是nivolumab治疗难治性转移性SCCA的首项前瞻性II期试验。单药nivolumab证明其有潜在活性而且耐受性良好。对转移性SCCA进行免疫检查点治疗的下一步评估是有道理的。更新的临床结果不久将会提交。探索性的相关工作正在进行中。临床试验信息：NCT02314169。
会议专题》》》2016年ASCO年会专题报道
原文摘要：
NCI9673: A multi-institutional eETCTN phase II study of nivolumab in refractory metastatic squamous cell carcinoma of the anal canal (SCCA).（Abstract3502）
Authors：Van Karlyle Morris, Kristen Keon Ciombor,et al.
Session Type：Oral Abstract Session
Background: The incidence of SCCA continues to rise annually in the US. 20% of patients (pts) will develop metastatic (met) disease which lacks a consensus approach to treatment. SCCA is largely driven by immune evasion of HPV-specific CD8 and CD4 T cells which promote oncogenesis for SCCA. Nivolumab (Nivo), a monoclonal antibody targeting PD-1 on T cells, promotes immune-mediated anti-tumor activity of T cells against HPV-positive cells in vitro. This is the first phase II trial of Nivo for pts with refractory met SCCA.
Methods: Previously treated but immunotherapy naïve met SCCA pts were eligible. PD-L1 expression was not required. HIV+ (CD4 count > 300/uL) and hepatitis B/C pts were eligible. A Simon two-stage phase II trial (Ho: p < .05, Ha: p ≥ .20) was conducted. All pts were evaluated by RECIST Criteria 1.1. Pts received Nivo (3 mg/kg) IV every 2 weeks. Optional pre-treatment and on-treatment tissue biopsies and plasma samples were collected for immune biomarkers and HPV/p16 status. All correlatives were evaluated at MDACC by the Immunotherapy Platform team and the Core Facility.
Results: 39 pts were screened across the ETCTN network (May 2015 - October 2015); 37 pts were eligible. Median age was 56 years (interquartile range [IQR], 51.1-63.6); M:F was 12:25. Median number of prior therapies: 2 (range 1-8). All pts were evaluable for toxicity; 33 pts were evaluable for response. Median number of cycles: 6 (IQR, 3-10). Seven (21%) pts had a partial response and 19 (58%) pts had stable disease; disease control rate of 79%. Ten pts (one HIV+) remain on study [7 pts for > 6 months (M)]. Median progression-free survival was 4.1M. Common adverse events (AE): fatigue, nausea, and rash. Six pts had grade 3 AE’s: fatigue (N = 2) and one pt each of pneumonitis, rash, anemia, and hyperglycemia.
Conclusions: Currently, there is no consensus approach for met SCCA. NCI9673 is the first prospective phase II trial of nivolumab in refractory metastatic SCCA. Single agent nivolumab demonstrated potentially meaningful activity and was well tolerated. Further evaluation of immune checkpoint therapy in met SCCA is justified. Updated clinical results will be presented. Exploratory correlative work is ongoing. Clinical trial information: NCT02314169
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