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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）年会将在芝加哥举办。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3501的CheckMate-142中期试验，将Nivolumab±ipilimumab治疗高度微卫星不稳定（MSI-H）的转移性结直肠癌（mCRC）患者和非-MSI-H表型的mCRC患者的数据进行讨论，医脉通整理如下：

目前证据支持nivolumab（N）用于MSI-H表型mCRC的治疗。Nivolumab，一种全人源化抗-PD-1单克隆抗体和ipilimumab（I），一种人源化抗-CTLA-4单克隆抗体，在其他肿瘤中有良好的安全性和有效性。CheckMate-142，一项2期研究，在MSI-H表型和非-MSI-H表型的mCRC患者中对N±I疗效进行评估。

患者ECOG PS评分为0-1，同时对至少1次以上治疗不耐受/进展。MSI-H表型mCRC患者接受N 3mg/kg q2 wk（N3）或者N 3mg/kg+I 1mg/kg q3 wk（N3+I1）×4次剂量序贯N3直到疾病进展（PD）或者其他原因停药。N+I3次剂量的初步评估在非-MSI-H表型mCRC患者中完成。主要终点是研究人员根据RECIST 1.1报道的ORR；其他终点是安全性，OS，和PFS。

一共有33例（N3）和26例（N3+I1）MSI-H表型患者，和3例（N1+I1），10例（N1+I3），和10例（N3+I1）的非-MSI-H表型患者入组。82%（N3）和92%（N3+I1）的MSI-H表型以及100%的非-MSI-H表型患者接受过≥2次方案。15%（N3）和25%（N3+I1）的MSI-H表型患者是已知的BRAF V600E。17例（52%；N3）和19例（73%；N3+I1）MSI-H表型患者仍在治疗中。有效性结果如表所示。

在MSI-H表型患者中，治疗相关的不良事件（TRAEs）发生在26例（79%；N3）和22例（85%；N3+I1）患者中；最常见的是腹泻和疲劳（每种27%；N3）以及腹泻（46%；N3+I1）。3-4级TRAEs发生在7例（N3）和8例（N3+I1）患者中。1例接受N3的患者出现5级TRAE（猝死）。在非-MSI-H表型患者中中位PFS（95% CI）是1.4个月（1.2-1.9；汇总N+I）。

综上所述，在大多数患者中，Nivolumab和Nivolumab+ipilimumab方案耐受性良好，并在MSI-H表型mCRC患者中表现出可喜的临床活性和生存期。这项研究正在进行中。临床试验信息：NCT02060188。

会议专题》》》2016年ASCO年会专题报道

原文摘要：

Nivolumab ± ipilimumab in treatment (tx) of patients (pts) with metastatic colorectal cancer (mCRC) with and without high microsatellite instability (MSI-H): CheckMate-142 interim results（Abstract3501）

Authors：Michael J.Overman, Scott Kopetz,et al.

Session Type：Oral Abstract Session

Background: Evidence supports use of nivolumab (N) in MSI-H mCRC. N, a fully human anti-PD-1 mAb and ipilimumab (I), a humanized anti-CTLA-4 mAb, have favorable safety & efficacy in other tumors. CheckMate-142, a phase 2 study, evaluates N ± I in pts with mCRC, MSI-H and non-MSI-H. 

Methods: Pts had ECOG PS 0–1, and intolerance/progression on ≥ 1 tx. MSI-H pts received N 3 mg/kg q2 wk (N3) or N 3 mg/kg + I 1 mg/kg q3 wk (N3+I1) x 4 doses followed by N3 until disease progression (PD) or other discontinuation. Initial evaluation of N+I at 3 doses was completed in non-MSI-H pts. Primary endpoint was investigator-reported ORR by RECIST 1.1; other endpoints were safety, OS, and PFS. 

Results: 33 (N3) and 26 (N3+I1) MSI-H pts, and 3 (N1+I1), 10 (N1+I3), and 10 (N3+I1) non-MSI-H pts were enrolled. 82% (N3) and 92% (N3+I1) of MSI-H and 100% of non-MSI-H pts had ≥ 2 prior regimens. 15% (N3) and 25% (N3+I1) of MSI-H pts had known BRAF V600E. 17 (52%; N3) and 19 (73%; N3+I1) MSI-H pts remain on tx. Efficacy results are shown in the Table. In MSI-H pts, tx-related adverse events (TRAEs) occurred in 26 (79%; N3) and 22 pts (85%; N3+I1); most common were diarrhea and fatigue (27% each; N3) and diarrhea (46%; N3+I1). Grade 3–4 TRAEs occurred in 7 (N3) and 8 pts (N3+I1). One pt on N3 had a Grade 5 TRAE (sudden death). In non-MSI-H pts median (95% CI) PFS was 1.4 mo (1.2–1.9; pooled N+I). 

Conclusions: N and N+I were well tolerated in most pts and demonstrated encouraging clinical activity and survival in MSI-H mCRC. This study is ongoing. Clinical trial information: NCT02060188

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