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Codon-specific KRAS mutations predict survival in advanced pancreatic cancer

A Boilève1,2,3, A Rousseau3,4,5, M Hilmi6

  • 1INSERM U1279, Gustave Roussy, Villejuif.

ESMO Gastrointestinal Oncology
|February 6, 2026
PubMed
Abstract

Insights

Patients with KRAS G12 mutations in pancreatic cancer have a worse prognosis than those with other KRAS mutations. This highlights the importance of specific KRAS alterations in pancreatic ductal adenocarcinoma (PDAC) outcomes.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • The impact of distinct KRAS alterations on pancreatic adenocarcinoma (PDAC) initiation and outcomes is not well understood.
  • Novel KRAS G12 inhibitors are emerging, but patient subgroup outcomes require further description.
  • This study investigates differences between codon-specific KRAS mutations (G12 vs. others) in PDAC.

Purpose of the Study:

  • To compare clinical and genomic characteristics of PDAC patients based on codon-specific KRAS mutations.
  • To analyze gene expression profiles and in vitro drug sensitivity in different KRAS mutation groups.
  • To evaluate the prognostic significance of KRAS G12 versus other KRAS mutations in PDAC.

Main Methods:

  • Retrospective analysis of metastatic PDAC patients with available molecular profiles (2015-2022).
  • Inclusion of patients with KRAS mutations; transcriptomic data analyzed from 69 tumors.
  • Comparison of clinicopathological features, actionable alterations, survival, and treatment response between KRAS G12 and KRAS other groups.

Main Results:

  • 263 patients included: 239 KRAS G12 (91%) and 24 KRAS other (9%).
  • No significant differences in clinicopathological characteristics or actionable alterations, except BRAF (p=0.01) and GNAS (p=0.002) in KRAS other.
  • Median overall survival was significantly longer for KRAS other (24.9 months) vs. KRAS G12 (16.7 months) (HR=0.56, p=0.04 adjusted); immune pathways were upregulated in KRAS G12 tumors.

Conclusions:

  • Codon-specific KRAS mutations have unequal prognostic implications in PDAC.
  • KRAS G12 patients exhibit a worse prognosis compared to KRAS other patients.
  • Further large-scale studies are warranted to confirm these findings.
Keywords:
KRASpancreatic cancerprecision medicine

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