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Published on: August 11, 2017
The IASLC grading system as a predictor for EGFR-TKI therapy in patients with EGFR-mutant lung adenocarcinoma
Chaoqiang Deng1,2,3, Molin Zhang1,2,3, Fangqiu Fu1,2,3
1Department of Thoracic Surgery and State Key Laboratory of Genetics and Development of Complex Phenotypes, Fudan University Shanghai Cancer Center, Shanghai, China.
Background:
We previously validated the grading system proposed by International Association for the Study of Lung Cancer (IASLC) for invasive nonmucinous lung adenocarcinoma (LADC) for its reproducibility, prognostication function and predictive value of adjuvant chemotherapy (ACT). In this exploratory study, we aimed to investigate the role of IASLC grading system in EGFR tyrosine kinase inhibitor (TKI) therapy selection either as adjuvant or palliative therapy.
Methods:
From 2008 to 2021, a cohort of 2,160 patients with invasive nonmucinous EGFR-mutant LADCs were retrospectively collected and classified according to the IASLC grading system. Clinical follow-up data for adjuvant EGFR-TKI treatment in stage Ib-III LADCs, and systemic EGFR-TKI treatment after tumor relapse were collected for prognostic evaluation. Next-generation sequencing (NGS) was carried out for 1158 cases which provided co-occurring mutation information.
Results:
EGFR exon 19 deletion was significantly more prevalent in IASLC high grade adenocarcinomas while L858R did the opposite (P<0.001). Patients with IASLC grade 3 adenocarcinoma (but not grade 1-2 adenocarcinoma) derived disease-free survival (DFS) benefit from adjuvant EGFR-TKIs in comparison to ACT (P=0.007). This remained significant after adjustment for tumor stages [hazard ratio (HR) 0.74, 95% confidence interval (CI): 0.56-0.98, P=0.04]. In addition, high grade patients had a significant benefit for both progression-free survival (PFS) and overall survival (OS) upon EGFR-TKI treatment after tumor relapse. Co-mutations such as TP53 mutations occurred more frequently in high grade adenocarcinomas, with no detrimental effect on TKI efficacy observed.
Conclusions:
This retrospective study first revealed the feasibility of IASLC grading system as a potential prediction factor for EGFR-TKIs therapy in patients with EGFR-mutant adenocarcinoma.
