2024 Targeted Therapies for Lung Cancer (TTLC) - Abstracts & Posters-PP01.01 Conroy

PP01.01 Conroy - Abstract

Pdf Summary

Plasma comprehensive genomic profiling (pCGP) was utilized to identify actionable mutations and mechanisms of resistance to EGFR targeted therapy in lung cancer patients. A study conducted at the Johns Hopkins University School of Medicine analyzed pCGP data from 818 patients with non-small cell lung cancer (NSCLC) between 2015-2022. Of the patients analyzed, 36% had FDA-approved actionable alterations at first diagnosis, including mutations in EGFR, KRAS, ALK, MET, ERBB2, BRAF, RET, and ROS1. Among patients with EGFR-mutant NSCLC, different mutation patterns were observed, with varying responses to first/second and third-generation TKIs. Resistance mechanisms post-treatment included T790M mutations, C797S mutations, and novel mutations in the EGFR kinase domain. Additionally, PIK3CA mutations, MET amplifications, and ERBB2 alterations were identified as potential resistance mechanisms to EGFR TKIs. Overall, 18% of pretreated patients with pCGP had resistance mutations with FDA-approved therapies, and 22% had actionable findings at progression. The study concluded that pCGP can identify actionable targets in NSCLC patients at diagnosis and resistance mechanisms post-EGFR TKI treatment, with divergent pathways seen between different generations of TKIs. The utility of pCGP in identifying oncogenic fusions as resistance mechanisms was found to be less significant.

Keywords

Plasma comprehensive genomic profiling

pCGP

actionable mutations

resistance mechanisms

EGFR targeted therapy

lung cancer patients

non-small cell lung cancer

NSCLC

EGFR mutations

TKIs