Abstract 166P
Background
The clinical benefits of immunotherapy are limited for unselected EGFR+ lung adenocarcinoma (LUAD). Conventional biomarkers like PD-L1 or TMB are not sufficient for these patients. Additionally, efficacy of EGFR-TKIs among EGFR+/TP53+ patients are significantly inferior to EGFR+/TP53- patients and subsequent treatment strategy are even more important. We conducted an integrated analysis to investigate the influence of TP53 mutation in immunotherapy efficacy and tumor microenvironment (TME) among EGFR+ LUAD.
Methods
A retrospective study was conducted to explore the predictive value of TP53 in clinical outcomes of immunotherapy. Analyses of genomic and transcriptomic data from TCGA database and immunohistochemistry results of tumor infiltrating immune cells (TIICs) from paired samples at baseline and after resistance to EGFR-TKIs from the local cohort were conducted to explore the changes in TME.
Results
A total of 42 EGFR+ LUAD patients were included in the retrospective study. The median PFS of TP53+ patients was significantly longer than that of TP53- patients (6.7 vs. 2.6 months; p= 0.003). Multivariate Cox regression analysis indicated that only TP53 mutation was significantly associated with superior PFS (HR, 0.38; 95%CI, 0.17-0.84; p = 0.016). TCGA data analysis indicated that there were no significant differences in PD-L1 expression, TMB and fractions of TIICs between TP53+ and TP53- groups. Among local cohort, there were also no significant differences in tumor infiltrating immune cells between TP53+ and TP53- patients in both baseline and re-biopsy samples. However, analysis of 20 paired samples revealed that the median density of CD8+ T cell increased significantly during EGFR-TKI treatment only in TP53+ patients (re-biopsy vs. baseline: 14.6 vs. 3.2; p = 0.008), not in TP53- patients (21.9 vs. 13.6; p = 0.422).
Conclusions
TP53 mutation is an independent predictive factor of superior efficacy of anti-PD-1/PD-L1 treatment among EGFR+ LUAD patients, which may result from the trend to be more inflamed in TME during EGFR treatment among TP53+ patients.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.