443O - EGFR mutations are associated with unfavourable efficacy to anti-PD1 therapy in NSCLC

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Thoracic cancers
Topics Biomarkers
Non-Small-Cell Lung Cancer, Metastatic
Cancer Immunology and Immunotherapy
Presenter Si-Yang Liu
Citation Annals of Oncology (2016) 27 (suppl_9): ix139-ix156. 10.1093/annonc/mdw594
Authors S. Liu1, Z. Dong1, W. Zhong1, Y. Wu2
  • 1Guangdong Lung Cancer Institute, Guangdong General Hospital, 510080 - Guangzhou/CN
  • 2Lung Cancer, Guangdong General Hospital, 510080 - Guangzhou/CN

Abstract

Background

Along with the development of targeted therapies and immunotherapy, the management of NSCLC is facing a tremendous changing. However, only 20% patients could benefit from PD-1 inhibitors. The precise biomarker in immunotherapy remains exclusive now. Furthermore, unlike targeted therapies the role of genetic alterations in oncogenic drivers remains unclear in anti-PD1 therapy. Here we conducted this data analysis to find out whether EGFR mutant status would have an influence on immunotherapy and how it works in NSCLCs.

Methods

A meta-analysis was conducted from data of EGFR mutant patients enrolled in CheckMate 057 and Keynote 010. Furthermore we analyzed 462 patients with lung adenocarcinoma from TCGA to investigate the mechanisms, such as nonsynonymous mutation counts, incidence of MMR (mis-match repair)-related gene mutations and the content of CD8 TILs.

Results

1543 NSCLC patients were enrolled in our meta-analysis, of which 168 harbored EGFR mutations. We can see EGFR mutant patients showed worse efficacy of anti-PD1 therapy compared with chemotherapy on PFS (hazard ratio [HR] 1.57, 95% CI 1.07 – 2.31, p = 0.02), while EGFR-wild patients treated with anti-PD1 therapy had significantly longer PFS (hazard ratio [HR] 0.83, 95% CI 0.73 – 0.94, p = 0.004) (Fig. 1). Moreover for OS, EGFR mutant patients received anti-PD1 therapy presented a slightly increase in the relative risk of death (HR 1.05, 95% CI 0.69 – 1.60, p = 0.81), while a 33% decrease was observed in EGFR-wild patients (HR 0.67, 95% CI 0.58 – 0.77, p 

Conclusions

Our study indicated that EGFR mutant patients may not be an appropriate subtype to receive immunotherapy partly because of weak immunogenicity and lower content of CD8+ CTL. Further prospective studies to confirm these observations are necessary

Clinical trial indentification

Legal entity responsible for the study

N/A

Funding

Guangdong Provincial Key Laboratory of Lung Cancer translational Medicine (Grant No. 2012A061400006)

Disclosure

All authors have declared no conflicts of interest.