172P - T cell-derived circulating DNA and tumour inflammatory microenvironment in EGFR-mutant advanced non-small cell lung cancer: Correlation with the outcome of EGFR TKI treatment

Background

We previously reported paradoxical impact of T-cell derived circulating DNA (T-cirDNA) in-term of prognosis marker in advanced non-small cell lung cancer (NSCLC). Longer durability of EGFR tyrosine kinase inhibitor (EGFRi) was correlated with undetectable T-cirDNA/cirDNA. This study aimed to confirm the finding in a larger cohort, correlated with tumor immune microenvironment (TIME).

Methods

Pretreatment plasma of patients with advanced EGFR-mutant NSCLCs who received EGFRi were collected. The semi-quantitative T-cirDNA /cirDNA was conducted by multiplex real-time polymerase chain reaction. Correlation with clinical outcome and TIME, including programmed cell death ligand-1 (PD-L1 clone 22C3), CD8 tumor infiltration lymphocyte (TIL), and Treg/FOXP3 were conducted.

Results

One-hundred and thirty-nine patients were divided according to T-cirDNA/cirDNA into undetectable (30%), low (≤1% ratio; 38.1%), and high (>1% ratio; 31.6%). The median progression-free survival (PFS) was 13.1 [95% CI 8.8 – 17.4], 9.0 [95% CI 6.7 – 12.5], and 13.2 [95% CI 8.8 – 19.3] months respectively, which was longest in undetectable and high T-cirDNA/cirDNA. Sixty-eight available tissue blocks for TIME study revealed decremental proportion of high PD-L1 (≥15% TPS) in high (21%), low (13%) and undetectable T-cirDNA/cirDNA (4%). While high intra-tumoral CD8 TIL (≥1%) had lowest proportion in low T-cirDNA/cirDNA (17%) contrary to undetectable (36%) and high T-cirDNA/cirDNA (47%). Multivariate cox-regression analysis revealed that high PD-L1 and high intra-tumoral CD8 TIL were independent factors correlated with shortened PFS. Good ECOG performance status (0-1) and undetectable T-cirDNA/cirDNA were solely independent prognostic factor to overall survival.

Conclusions

Undetectable T-cirDNA/cirDNA represents inactivated naïve T-cell and indicated favorable prognosis in EGFR-mutant NSCLCs who received EGFRi. Inflammatory TIME including high PD-L1 and high intra-tumoral CD8 indicated shorted disease control with EGFRi. The interaction of active T-lymphocyte and TIME in EGFR alteration advanced NSCLC received EGFRi is warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

The Health Systems Research Institute (Thailand).

Disclosure

N. Zungsontiporn: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Takeda. P. Sitthideatphaiboon: Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, Merck, Pfizer, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Novartis, Pfizer, Roche, Takeda; Financial Interests, Institutional, Local PI: AstraZeneca, Roche, Merck, Novartis. K. Korphaisarn: Financial Interests, Personal, Invited Speaker: Roche, Amgen, AstraZeneca, MSD; Non-Financial Interests, Principal Investigator: MSD, Roche. V. Sriuranpong: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Novartis, MSD, Pfizer, Amgen; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Novartis, MSD, Amgen; Financial Interests, Institutional, Research Funding: Roche, AstraZeneca, Novartis, MSD, Amgen. All other authors have declared no conflicts of interest.