Clinical outcomes and predictive value of programmed cell death-ligand 1 expression in response to anti-programmed cell death 1/ligand 1 antibodies in non-small cell lung cancer patients with performance status 2 or greater

Int J Clin Oncol. 2021 Jan;26(1):78-86. doi: 10.1007/s10147-020-01789-5. Epub 2020 Sep 23.

Abstract

Background: Anti-programmed cell death protein-1/ligand-1 (anti-PD-1/PD-L1) therapy is promising for patients with non-small-cell lung cancer (NSCLC); however, clinical trials have focused on patients with a performance status (PS) 0 or 1. This study aimed to evaluate the clinical outcomes and correlation between PD-L1 expression status and tumor response to anti-PD-1/PD-L1 therapy among NSCLC patients with poor PS (i.e., PS ≥ 2).

Methods: In total, 130 patients with NSCLC and PS ≥ 2 treated with anti-PD-1/PD-L1 monotherapy at 12 institutions between January 2016 and August 2019 were retrospectively reviewed. PD-L1 expression status was divided into four groups: < 1%, 1-49%, ≥ 50%, and unknown.

Results: The objective response rate and PS improvement rate were 23 and 21% and were higher in the PD-L1 ≥ 50% group than in other groups (P < 0.01). Median progression-free survival (PFS) was 62 days and was longer in the PD-L1 ≥ 50% group than in other groups (P = 0.03). Multivariate analyses revealed that PD-L1 expression is significantly associated with prolonged PFS (PD-L1 < 1%; reference; 1-49%, hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.04-0.99, P = 0.05; ≥ 50%, HR 0.12, 95% CI 0.02-0.71, P = 0.02; unknown, HR 0.30, 95% CI 0.08-1.22, P = 0.09).

Conclusions: NSCLC patients with poor PS and PD-L1 ≥ 50% are expected to benefit from anti-PD-1/PD-L1 therapy, despite a modest overall response among NSCLC patients with poor PS. Accordingly, PD-L1 expression provides useful information regarding decision-making for anti-PD-1/PD-L1 therapy even in these populations.

Keywords: Anti-programmed cell death protein-1/ligand-1 therapy; Non-small cell lung cancer; Performance status; Programmed cell death-ligand 1 expression.

MeSH terms

  • Antineoplastic Agents, Immunological* / therapeutic use
  • Apoptosis
  • B7-H1 Antigen
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Humans
  • Ligands
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Retrospective Studies

Substances

  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • Ligands