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<p><i>KRAS</i> and <i>BRAF</i><sup><i>V600E</i></sup> mutations are established biomarkers in metastatic colorectal cancer (CRC), but their predictive roles in early-stage disease remain uncertain. We aimed to determine whether <i>KRAS</i> and <i>BRAF</i><sup><i>V600E</i></sup> mutations modify the association between adjuvant chemotherapy regimen and survival in stage III and high-risk stage II CRC. We analyzed patients who underwent curative resection and molecular profiling for <i>KRAS</i> and <i>BRAF</i><sup><i>V600E</i></sup>. Adjuvant chemotherapy was classified as fluoropyrimidine monotherapy (5FU) or oxaliplatin-based therapy (Ox+). Propensity score overlap weighting addressed non-randomized treatment allocation. Weighted Cox models assessed recurrence-free survival (RFS) and overall survival (OS), including tests for treatment-by-mutation interaction. Among treated patients (<i>n</i> = 853), a global interaction test indicated a differential association between regimens and survival by mutation status (OS, <i>p</i> = 0.007; RFS <i>p</i> = 0.049). Ox+ was associated with improved survival in patients with <i>KRAS</i>-mutated tumors (OS HR = 0.68, 95% CI, 0.47–0.98), and a less favorable outcome in <i>BRAF</i>-mutated tumors (OS HR = 2.58, 95% CI, 1.16–5.77) compared with 5FU. Outcomes were similar between Ox+ and 5FU in double wild-type (<i>KRAS</i> and <i>BRAF</i> wild-type) tumors (OS HR = 1.11, 95% CI, 0.82–1.50). These findings suggest molecular heterogeneity in treatment associations that may inform adjuvant therapy selection.</p>

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KRAS and BRAF mutations modify adjuvant chemotherapy outcomes in early stage colorectal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月20日

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  • Durgesh Wankhede,
  • Mary Jose Urruchua Rodriguez,
  • Dominic Edelmann,
  • Matthias Kloor,
  • Hendrik Bläker,
  • Alexander Brobeil,
  • Wilfried Roth,
  • Hermann Brenner,
  • Michael Hoffmeister

摘要

KRAS and BRAFV600E mutations are established biomarkers in metastatic colorectal cancer (CRC), but their predictive roles in early-stage disease remain uncertain. We aimed to determine whether KRAS and BRAFV600E mutations modify the association between adjuvant chemotherapy regimen and survival in stage III and high-risk stage II CRC. We analyzed patients who underwent curative resection and molecular profiling for KRAS and BRAFV600E. Adjuvant chemotherapy was classified as fluoropyrimidine monotherapy (5FU) or oxaliplatin-based therapy (Ox+). Propensity score overlap weighting addressed non-randomized treatment allocation. Weighted Cox models assessed recurrence-free survival (RFS) and overall survival (OS), including tests for treatment-by-mutation interaction. Among treated patients (n = 853), a global interaction test indicated a differential association between regimens and survival by mutation status (OS, p = 0.007; RFS p = 0.049). Ox+ was associated with improved survival in patients with KRAS-mutated tumors (OS HR = 0.68, 95% CI, 0.47–0.98), and a less favorable outcome in BRAF-mutated tumors (OS HR = 2.58, 95% CI, 1.16–5.77) compared with 5FU. Outcomes were similar between Ox+ and 5FU in double wild-type (KRAS and BRAF wild-type) tumors (OS HR = 1.11, 95% CI, 0.82–1.50). These findings suggest molecular heterogeneity in treatment associations that may inform adjuvant therapy selection.