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Efficacy of first-line immunochemotherapy across KRAS mutation subtypes in advanced lung adenocarcinoma

Hongping Jin1, Honglei Huang2, Yiqing Wu1

  • 1Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

International Journal of Cancer
|February 4, 2026
PubMed

Insights

First-line immunochemotherapy shows similar effectiveness for advanced lung adenocarcinoma patients with different KRAS mutations, regardless of PD-L1 expression. STK11 co-mutations were linked to poorer outcomes.

Area of Science:

  • Oncology
  • Genetics
  • Immunotherapy

Background:

  • KRAS mutations are common in lung adenocarcinoma (LUAD).
  • The impact of specific KRAS subtypes on treatment response to first-line immunochemotherapy is not well understood.
  • Programmed death-ligand 1 (PD-L1) expression and co-mutations may influence treatment efficacy.

Purpose of the Study:

  • To evaluate the treatment efficacy of first-line immunochemotherapy across different KRAS mutation subtypes in advanced LUAD.
  • To examine the role of PD-L1 expression and co-mutations in predicting treatment response.

Main Methods:

  • Retrospective analysis of 335 advanced KRAS-mutant LUAD patients treated with first-line immunochemotherapy.
  • Categorization of patients based on KRAS subtypes (G12A, G12C, G12D, G12V, and others).
  • Stratification of PD-L1 tumor proportion score (TPS) and assessment of co-mutations, including STK11.

Main Results:

  • Overall median progression-free survival (PFS) was 8.6 months, with an objective response rate (ORR) of 34.0% and disease control rate (DCR) of 87.8%.
  • No significant differences in PFS were observed among KRAS subtypes or across PD-L1 TPS groups (<1%, 1-49%, ≥50%).
  • STK11 co-mutations were more frequent in G12C, G12V, and other KRAS subtypes and were associated with shorter PFS.

Conclusions:

  • First-line immunochemotherapy demonstrates comparable efficacy across various KRAS mutation subtypes in advanced LUAD, irrespective of PD-L1 expression levels.
  • PD-L1 expression did not predict PFS within major KRAS subgroups.
  • STK11 co-mutations represent a potential negative prognostic factor in this patient population.
Keywords:
KRASPD‐L1co‐mutationsimmunochemotherapylung adenocarcinoma

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