2025 Targeted Therapies of Lung Cancer (TTLC) - Posters-PP01.02 Genomic and Clinical Heterogeneity of Patients with Non-Small Cell Lung Cancer Tumors Harboring PIK3CA Mutations

PP01.02 Genomic and Clinical Heterogeneity of Patients with Non-Small Cell Lung Cancer Tumors Harboring PIK3CA Mutations

Back to course

Pdf Summary

The study analyzes the clinico-genomic characteristics of non-small cell lung cancer (NSCLC) tumors with PIK3CA mutations, which occur in 5-8% of such cancers and activate the PI3K/Akt/mTOR pathway, promoting tumor growth. While PI3K inhibitors are FDA-approved for other cancers with PIK3CA mutations, they have shown limited success in NSCLC due to the molecular heterogeneity of PIK3CA mutations in these tumors.<br /><br />Data from the AACR Project GENIE database was used to compare NSCLC tumors with PIK3CA mutations paired with or without other canonical driver mutations, like EGFR, ALK, ROS1, among others. The study focused on tumors with PIK3CA mutations lacking other driver mutations (PIK3CAmut/driver-) regarding their genomic features and response to first-line chemotherapy or immunotherapy.<br /><br />The study found that helical domain mutations (HDM) and kinase domain mutations (KDM) are common, with the former being more prevalent in PIK3CAmut/driver- tumors. PIK3CAmut/driver- tumors were often associated with factors like being male, squamous cell carcinoma type, and non-Asian ethnicity.<br /><br />Co-mutations in tumor suppressor genes like TP53, STK11, and RB1 were more frequent among PIK3CAmut/driver- adenocarcinomas. Advanced PIK3CAmut/driver- NSCLC cases showed poor progression-free survival (PFS) and overall survival (OS) metrics upon first-line treatment.<br /><br />PIK3CA mutations independently exist in some NSCLC tumors, and their presence without other known drivers suggests a distinct molecular subset. This finding emphasizes the need for optimizing patient selection in PI3K-inhibitor trials for NSCLC to address the poor outcomes associated with uncommon PIK3CA mutations, suggesting targeted strategies for such molecular profiles in future cancer therapy assessments.

Asset Subtitle

Yu-Cheng Chang

Keywords

NSCLC

PIK3CA mutations

PI3K/Akt/mTOR pathway

PI3K inhibitors

molecular heterogeneity

helical domain mutations

kinase domain mutations

tumor suppressor genes

progression-free survival

targeted cancer therapy