WCLC 2025 - Posters & ePosters-P1.11.30 The Efficacy of Immunotherapyfor Patients With Advanced Lung Cancer and Oncogenic Driver Alterations

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This study investigated the efficacy of immune checkpoint inhibitors (ICIs) in 407 patients with advanced non-small-cell lung cancer (NSCLC) harboring various oncogenic driver mutations, including KRAS, EGFR, BRAF, MET, HER2, ALK, RET, and ROS1. While ICIs targeting the PD-1/PD-L1 axis are standard for advanced NSCLC without driver mutations, their effectiveness in tumors with such genetic alterations remains unclear.<br /><br />Among the cohort, 35.9% received ICIs after progression on prior tyrosine kinase inhibitor therapy, mainly within the EGFR subgroup, while 64.1% received ICIs as first-line treatment predominantly in the KRAS subgroup. Overall, the median progression-free survival (PFS) was 17.0 months, with mutation-specific median PFS ranging from 6.4 months in ALK-mutant to over 31 months in BRAF- and RET-mutant tumors. Notably, PD-L1 expression significantly correlated with longer PFS only in KRAS-mutant tumors, but not in EGFR-mutant tumors.<br /><br />RNA sequencing analysis of tumor samples from The Cancer Genome Atlas revealed that KRAS- and BRAF-mutant tumors exhibited higher expression of immune effector genes and greater enrichment in antitumor immune pathways, such as CD8 T cell and immune checkpoint activation. Conversely, tumors with EGFR, ALK, RET, MET, and ROS1 alterations showed reduced immune gene expression. A meta-analysis of 13 studies supported these findings by demonstrating the highest objective response rates in KRAS- and BRAF-mutant NSCLC patients treated with ICIs.<br /><br />The study highlights the heterogeneous response to ICIs among NSCLC patients with different driver mutations and suggests that oncogenic alterations influence the tumor immune microenvironment and therapeutic outcomes. Integrating comprehensive genomic profiling in clinical practice may enable precision oncology approaches, optimizing patient selection for ICIs and improving survival outcomes in this genetically diverse population.

Asset Subtitle

Jiaxin Zhong

Meta Tag

Speaker Jiaxin Zhong

Topic Metastatic Non-small Cell Lung Cancer – Immunotherapy

Keywords

immune checkpoint inhibitors

non-small-cell lung cancer

oncogenic driver mutations

KRAS mutation

EGFR mutation

PD-L1 expression

progression-free survival

RNA sequencing

tumor immune microenvironment

precision oncology