In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 9044-9044
Abstract:
9044 Background: Programmed death ligand-1 (PD-L1) expression is not a completely reliable predictive marker of the efficacy of anti-programmed cell death protein-1 (PD-1)/anti-PD-L1 therapy in advanced non-small cell lung cancer patients (NSCLC). Immune-related tumor microenvironment (TME) is classified into four different types based on the status of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression. Methods: We retrospectively reviewed advanced NSCLC patients treated with anti-PD-1/anti-PD-L1 therapy between 2015 and 2019, and investigated the association between the efficacy of anti-PD-1/anti-PD-L1 therapy, the types of TME based on PD-L1 (clone: 22C3) expression, and the density of CD8-positive TILs by immunohistochemistry (/mm 2 ), and mutational profiles assessed by next-generation sequencing. Results: Overall, 228 patients without driver mutation ( EGFR, ALK, ROS1, and RET) were included in the analysis. The patients were classified into four following groups: Type I: PD-L1 High (tumor proportion score [TPS]≥50%)/TIL High (≥85/mm 2 ; n = 73), Type II: PD-L1 Low (TPS 〈 50%)/TIL Low ( 〈 85/mm 2 ; n = 70), Type III: PD-L1 High /TIL Low (n = 37), and Type IV: PD-L1 Low /TIL High (n = 48). The progression-free survival (PFS) and objective response rate (ORR) of anti-PD-1/anti-PD-L1 therapy clearly differed according to the different tumor microenvironment (TME) types (ORR and median PFS; Type I: 64%, 14.5 months, Type II: 12%, 2.1 months, Type III: 24%, 3.6 months, Type IV: 41%, 10.8 months). In patients with PD-L1 High tumors, Type I tumors had significantly better ORR and PFS than Type III (ORR: p 〈 0.001, and PFS: p 〈 0.001) tumors. Regarding the association between mutational profiles, histology and the TME types, the presence of TP53 mutation and KRAS mutation significantly related to TIL High (Type I and IV) and PD-L1 High tumors (Type I and III), respectively. Pleomorphic and NSCLC- not otherwise specified histology were associated with Type I tumors, while LCNEC was associated with PD-L1 low tumors (Type II and IV). Conclusions: Various factors (mutational profile and histology) are related to TME classification based on the status of TILs and PD-L1 expression. Differential types of TME, including PD-L1 expression and TILs status, can accurately predict the efficacy of anti-PD-1/anti-PD-L1 therapy.[Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2021.39.15_suppl.9044
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2021
detail.hit.zdb_id:
2005181-5
