Scholarlink

<p>Nivolumab alone and in combination with ipilimumab demonstrated durable clinical benefit in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer in the phase 2 CheckMate 142 study. Here, we report exploratory biomarker analyses from CheckMate 142 evaluating associations between various tissue biomarkers and the efficacy of nivolumab monotherapy and nivolumab plus ipilimumab combination in these patients. Higher expression of inflammation-related gene expression signatures is associated with improved response per investigator assessment and survival benefit with nivolumab monotherapy. In contrast, higher tumor mutational burden, tumor indel burden, and degrees of microsatellite instability are associated with improved response per investigator assessment and survival benefit with nivolumab plus ipilimumab. While interpretation is limited by the exploratory nature of these analyses, they suggest that tumor antigenicity rather than baseline tumor inflammation might be important for the combinatorial efficacy. Validation of these findings in larger, randomized studies is necessary.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Inflammation and mutational burden differentially associated with nivolumab or ipilimumab combination efficacy in colorectal cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月6日

查看全文
  • Ming Lei,
  • Michael J. Overman,
  • Jin Yao,
  • Thierry André,
  • Sara Lonardi,
  • Heinz-Josef Lenz,
  • Massimo Aglietta,
  • Fabio Gelsomino,
  • Ray McDermott,
  • Ka Yeung Mark Wong,
  • Michael A. Morse,
  • Eric Van Cutsem,
  • Alain Hendlisz,
  • Dana B. Cardin,
  • Bart Neyns,
  • Andrew Hill,
  • Anuradha Krishnamurthy,
  • Franklin Chen,
  • Samith Kochuparambil,
  • Robert R. Jenq,
  • Sandzhar Abdullaev,
  • Beilei He,
  • Ruslan Novosiadly,
  • Scott Kopetz

摘要

Nivolumab alone and in combination with ipilimumab demonstrated durable clinical benefit in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer in the phase 2 CheckMate 142 study. Here, we report exploratory biomarker analyses from CheckMate 142 evaluating associations between various tissue biomarkers and the efficacy of nivolumab monotherapy and nivolumab plus ipilimumab combination in these patients. Higher expression of inflammation-related gene expression signatures is associated with improved response per investigator assessment and survival benefit with nivolumab monotherapy. In contrast, higher tumor mutational burden, tumor indel burden, and degrees of microsatellite instability are associated with improved response per investigator assessment and survival benefit with nivolumab plus ipilimumab. While interpretation is limited by the exploratory nature of these analyses, they suggest that tumor antigenicity rather than baseline tumor inflammation might be important for the combinatorial efficacy. Validation of these findings in larger, randomized studies is necessary.