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Background <p>The randomised METIMMOX trial evaluated short-course oxaliplatin-based chemotherapy alternating with nivolumab for metastatic microsatellite-stable/mismatch repair-proficient colorectal cancer. In a <i>post hoc</i> analysis, we investigated whether tumour mutations or patients’ systemic inflammation might provide insights into responsiveness to the METIMMOX regimen.</p> Methods <p>Patients received either oxaliplatin-based chemotherapy (control group) or alternating two cycles each of chemotherapy and nivolumab (experimental group), with progression-free survival (PFS) as the primary endpoint. Tumour biopsies were sequenced with the TruSight Oncology 500 assay.</p> Results <p>The median tumour mutational burden (TMB; in mutations/megabase) was 8 (range, 1–13). The experimental-arm patients with TMB ≥9 or <i>BRAF</i>-V600E mutation (<i>n</i> = 17) achieved median PFS of 19.8 months (95% confidence interval, 11.3–28.3), longer (<i>p</i> = 0.0090) than experimental-arm patients with TMB &lt; 9 not <i>BRAF</i>-V600E (<i>n</i> = 19) and control-arm patients with either TMB and <i>BRAF</i> status combination (<i>n</i> = 31). With TMB ≥9 or <i>BRAF</i>-V600E and normal, non-inflammatory level of C-reactive protein when starting nivolumab (<i>n</i> = 11), median PFS was 35.0 months (95% confidence interval, 6.8–63.0; <i>p</i> &lt; 0.0001).</p> Conclusions <p>TMB, somatic <i>BRAF</i> status and systemic inflammation should be prospectively investigated as practical biomarkers for predicting potential responsiveness to immune checkpoint inhibitors in metastatic microsatellite-stable/mismatch repair-proficient colorectal cancer.</p>

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Exploratory biomarkers for oxaliplatin-induced nivolumab responsiveness in metastatic microsatellite-stable colorectal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月23日

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  • Anne Hansen Ree,
  • Paula A. Bousquet,
  • Tina Visnovska,
  • Torben Lüders,
  • Benjamin P. Geisler,
  • Shixiong Wang,
  • Diana L. Bordin,
  • Hilde L. Nilsen,
  • Hanne M. Hamre,
  • Christian Kersten,
  • Eva Hofsli,
  • Marianne G. Guren,
  • Halfdan Sorbye,
  • Jens P. Berg,
  • Kjersti Flatmark,
  • Sebastian Meltzer

摘要

Background

The randomised METIMMOX trial evaluated short-course oxaliplatin-based chemotherapy alternating with nivolumab for metastatic microsatellite-stable/mismatch repair-proficient colorectal cancer. In a post hoc analysis, we investigated whether tumour mutations or patients’ systemic inflammation might provide insights into responsiveness to the METIMMOX regimen.

Methods

Patients received either oxaliplatin-based chemotherapy (control group) or alternating two cycles each of chemotherapy and nivolumab (experimental group), with progression-free survival (PFS) as the primary endpoint. Tumour biopsies were sequenced with the TruSight Oncology 500 assay.

Results

The median tumour mutational burden (TMB; in mutations/megabase) was 8 (range, 1–13). The experimental-arm patients with TMB ≥9 or BRAF-V600E mutation (n = 17) achieved median PFS of 19.8 months (95% confidence interval, 11.3–28.3), longer (p = 0.0090) than experimental-arm patients with TMB < 9 not BRAF-V600E (n = 19) and control-arm patients with either TMB and BRAF status combination (n = 31). With TMB ≥9 or BRAF-V600E and normal, non-inflammatory level of C-reactive protein when starting nivolumab (n = 11), median PFS was 35.0 months (95% confidence interval, 6.8–63.0; p < 0.0001).

Conclusions

TMB, somatic BRAF status and systemic inflammation should be prospectively investigated as practical biomarkers for predicting potential responsiveness to immune checkpoint inhibitors in metastatic microsatellite-stable/mismatch repair-proficient colorectal cancer.