1078P - Correlation between T cell immunity and EGFR-TKI treatment in patients harboring EGFR driver mutation

Background

Although osimertinib provides a longer survival time than first/second-generation EGFR tyrosine kinase inhibitor (TKI) for non-small cell lung cancer (NSCLC) harboring EGFR mutations, acquired resistance is inevitable. Since the time to acquire resistance to TKI is shorter for cancers with a higher mutational burden and mutations increase after TKI resistance is acquired, the acquired resistance mechanism depends primarily on acquired mutations. Although the cancer immunoediting theory indicates that the process of genetic mutation accumulation by cancer cells involves a conflict with T-cell immunity, which recognizes gene mutation products as neoantigens and destroys them, the relationship between TKI treatment effect and immunological response in patients with EGFR-bearing NSCLC is unknown.To identify the correlation between T-cell immunity and the duration of TKI response, we examined the peripheral blood mononuclear cells (PBMCs) of patients with lung cancer prior to osimertinib therapy.

Methods

This study included patients with NSCLC harboring EGFR mutations who received TKI treatment between November 2018 and October 2020 at Saitama Medical University. Peripheral blood samples were collected before and after 4 weeks of TKI treatment. Mass cytometry was used to analyze the EMRA, EM, CM, and naïve fractions of CD8⁺ T cells, CD62L^low effector cell fraction of CD4⁺ T cells, Th cluster fractions based on CXCR3, CCR4, and CCR6 chemokine expression, and molecular expression in each fraction.

Results

Forty-three patients were enrolled in the study. Their median age was 73 (range: 45–88) years. For 43 patients, the response rate was 58.1%, and the disease control rate was 74.4%. Thirty-eight patients receiving osimertinib could be compared PBMCs pre and post TKI treatment. We identified CXCR3⁺CCR4^-CCR6⁺ CD4⁺ T cells (Th1/17) as T-cell clusters with a significant positive correlation with PFS after EGFR-TKI treatment. In the Kaplan-Meier analysis, patients with a higher Th1/17 ratio also tended to have significantly better PFS (p=0.01) and longer OS (p=0.01).

Conclusions

T-cell immunity influences the time to acquire resistance after EGFR-TKI treatment. Pre-treatment Th1/17 assays before EGFR-TKI treatment can predict PFS.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Hiroshi Kagamu.

Funding

Boehringer Ingelheim GmbH.

Disclosure

A. Mouri: Non-Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Co., Ono Pharmaceutical Co., Chugai Pharmaceutical Co., AstraZeneca. K. kaira: Non-Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Chugai Pharmaceutical Co., Ono Pharmaceutical Co., Bristol-Myers Co., Boehringer Ingelheim GmbH; Non-Financial Interests, Personal and Institutional, Research Grant: AstraZeneca. O. Yamaguchi: Non-Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Co., Ono Pharmaceutical Co, Chugai Pharmaceutical Co., AstraZeneca, Eli Lilly & Co. H. Imai: Non-Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Co., Ono Pharmaceutical Co. K. Kobayashi: Non-Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. H. Kagamu: Non-Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim GmbH, Chugai Pharmaceutical Co, Ono Pharmaceutical Co, Bristol-Myers Co., AstraZeneca; Non-Financial Interests, Personal and Institutional, Research Grant: Boehringer Ingelheim GmbH. All other authors have declared no conflicts of interest.