Baseline PD-L1 expression and tumour-infiltrated lymphocyte status predict the efficacy of durvalumab consolidation therapy after chemoradiotherapy in unresectable locally advanced patients with non-small-cell lung cancer

Eur J Cancer. 2022 Feb:162:1-10. doi: 10.1016/j.ejca.2021.11.013. Epub 2021 Dec 20.

Abstract

Background: Chemoradiotherapy (CRT) followed by durvalumab treatment improved prognosis in unresectable locally advanced non-small-cell lung cancer (LA-NSCLC). This study aimed to evaluate whether the status of the immune-related tumour microenvironment (TME) at baseline associates with the efficacy.

Methods: This retrospective study evaluated immune-related TME factors, including programmed cell death ligand 1 (PD-L1) (clone: 22C3) expression on tumour cells and the density of CD8-positive tumour-infiltrating lymphocytes (TILs) at pre-CRT in patients with unresectable LA-NSCLC treated with CRT only (CRT alone group) and those treated with CRT followed by durvalumab (Durva group).

Results: A total of 551 patients were included (N = 113 in the Durva group). Progression-free survival (PFS) in the Durva group was significantly greater than that in the CRT alone group (not reached [NR] vs 12.9 months; p = 0.002). In the CRT alone group, neither PD-L1 expression nor TIL status affected PFS; in contrast, in the Durva group, high density of CD8-positive TILs (TILHigh ≥100/mm2) and PD-L1-positive expression (tumour proportion score ≥1%; PD-L1+) was significantly associated with longer PFS (TIL: NR vs 9.5 months; p = 0.002; and PD-L1: NR vs 7.7 months; p = 0.003). On the other hand, in patients with epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements, there was no significant difference in PFS between the groups (Durva vs CRT alone: 9.9 months vs 14.0 months; p = 0.77).

Conclusions: PD-L1+ and TILHigh at baseline could be predictive markers of the efficacy of CRT followed by durvalumab.

Keywords: CD8; Durvalumab; Locally advanced non-small-cell carcinoma; Tumour-infiltrated lymphocytes; and PD-L1 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal* / immunology
  • Antibodies, Monoclonal* / pharmacology
  • B7-H1 Antigen* / biosynthesis
  • B7-H1 Antigen* / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / immunology
  • Carcinoma, Non-Small-Cell Lung* / radiotherapy
  • Chemoradiotherapy
  • Consolidation Chemotherapy
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lymphocytes, Tumor-Infiltrating* / immunology
  • Prognosis
  • Retrospective Studies
  • Tumor Microenvironment

Substances

  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • CD274 protein, human
  • durvalumab