Abstract 717P
Background
Despite the use of EGFR-TKIs (epidermal growth factor receptor-tyrosine kinase inhibitors) prolonging the survival of non-squamous cell carcinoma (SqCC) EGFR-mutant non-small cell lung cancer (NSCLC) patients, there is considerable variation in response and overall survival among different patients after using EGFR-TKIs. Our study aimed to analyze the prognostic role of next-generation sequencing (NGS) in this population.
Methods
This retrospective hospital-based cohort study screened advanced non-SqCC EGFR-mutant NSCLC patients who received EGFR-TKIs and underwent upfront tissue or liquid NGS testing between December 2018 and January 2024. Gene alterations include mutations and amplification. CCND, CCNE, CTNNB1, CDK4, CDK6, and CDKN2A/B gene alterations were categorized into “cell cycle gene alterations.” Activation of the RAS–mitogen-activated protein kinase (MAPK) or RAS-PI3K pathways were classified into the “RAS-PI3K-AKT-RAF alterations”.
Results
A total of 66 patients were analyzed. The median age was 60 years, with females accounting for 59.1%. The usage proportions of first, second, and third-generation EGFR-TKIs were 15.2%, 39.4%, and 45.5%, respectively. The overall objective response rate was 56.1%. EGFR compound mutations were present in 13.6% of patients, EGFR amplification in 18.2%, RAS-PI3K-AKT-RAF alterations in 27.3%, cell cycle gene alterations in 28.8%, and TP53 alterations in 39.4%. PD-L1 expression greater than or equal to 50% was observed in 12.1% of patients. In the analysis of the objective response rate, multivariable analysis showed that RAS-PI3K-AKT-RAF alterations were associated with a lower response rate, with an odds ratio of 0.26 (95% CI 0.08-0.91, p=0.035). In the overall survival analysis, multivariable analysis indicated that patients with RAS-PI3K-AKT-RAF alterations had a worse prognosis, with a hazard ratio of 6.92 (95% CI 2.07-23.11, p=0.002).
Conclusions
In advanced non-SqCC EGFR-mutant NSCLC patients, NGS may help predict patient prognosis. RAS-PI3K-AKT-RAF alterations were present in 27.3% of patients and were associated with a poorer response to EGFR-TKIs and overall survival.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.