A retrospective analysis of immunotherapy in non-small cell lung cancer patients with targetable genetic mutations

Shiyu Zhang1, Jingwen Liu2, Jia Liu3

  • 1Department of Respiratory and Critical Care Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, P.R. China.

Medicine
|September 17, 2025
PubMed

Insights

Driver gene mutations in non-small cell lung cancer impact immunotherapy effectiveness. Certain mutations may hinder response, while others show benefits, necessitating personalized treatment strategies for optimal outcomes.

Area of Science:

  • Oncology
  • Immunotherapy
  • Genomics

Background:

  • Targeted therapy and immunotherapy have advanced non-small cell lung cancer (NSCLC) treatment.
  • The role of immunotherapy in patients with targetable oncogenes remains under investigation.
  • Understanding driver gene mutations is crucial for optimizing NSCLC immunotherapy.

Purpose of the Study:

  • To analyze the impact of driver gene mutations on immunotherapy efficacy in NSCLC.
  • To evaluate programmed death-ligand 1 (PD-L1) and tumor mutation burden (TMB) as predictive biomarkers across different mutation groups.
  • To differentiate the effects of mono-immunotherapy versus combined immunotherapy based on genetic profiles.

Main Methods:

  • Retrospective analysis of 926 NSCLC immunotherapy cases from public data.
  • Grouping cases based on driver gene status: negative, non-sensitive mutations, and sensitive mutations.
  • Assessment of immunotherapy response in relation to specific gene mutations (e.g., KRAS, BRAF, EGFR) and biomarkers (PD-L1, TMB).

Main Results:

  • Sensitive mutations (excluding KRAS, BRAF) generally reduced immunotherapy effectiveness.
  • Non-sensitive mutations, except for EGFR, showed immune benefits.
  • PD-L1 and TMB predictive efficacy varied between mono- and combined immunotherapy, requiring separate consideration.

Conclusions:

  • Specific driver gene mutations in NSCLC can influence immunotherapy response.
  • Treatment decisions for immunotherapy should account for individual patient mutation profiles.
  • Further large-scale studies are needed to validate these findings and refine clinical strategies for NSCLC immunotherapy.

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