Clinical impact of tumour burden on the efficacy of PD-1/PD-L1 inhibitors plus chemotherapy in non-small-cell lung cancer

Cancer Med. 2023 Jan;12(2):1451-1460. doi: 10.1002/cam4.5035. Epub 2022 Jul 18.

Abstract

Background: Programmed cell death 1 (PD-1)/programmed cell death ligand (PD-L1) inhibitors plus chemotherapy (ICI + Chemo) is the standard treatment for advanced non-small-cell lung cancer (NSCLC). However, the impact of tumour burden on the efficacy of ICI + Chemo remains unknown.

Methods: We retrospectively evaluated 92 patients with advanced NSCLC treated with ICI + Chemo. Tumour burden was assessed as the sum of the longest diameter of the target lesion (BSLD) and number of metastatic lesions (BNMLs). We categorised the patients into three groups based on the combined BSLD and BNML values.

Results: Sixty-eight patients (74%) had progressive disease or died. Forty-four patients (48%) in the low-BSLD group had a median progression-free survival (PFS) of 9.5 months, whereas patients in the high-BSLD group had a median PFS of 4.6 months (hazard ratio [HR] = 0.54, p = 0012). Twenty-five patients (27%) in the low-BNML group had a median PFS of 9.6 months, whereas patients in the high-BNML group had a median PFS of 6.5 months (HR = 0.51, p = 0.029). Low-BSLD and low-BNML were associated independently with improved PFS in multivariate analysis. Analysis of the tumour burden combined with BSLD and BNML revealed a trend towards improved PFS as the tumour burden decreased, with median PFS of 22.3, 8.7, and 3.9 months in the low- (N = 13), medium- (N = 42) and high-burden (N = 37) groups respectively.

Conclusions: Our findings demonstrated that a high tumour burden negatively impacts the efficacy of ICI + Chemo in patients with advanced NSCLC.

Keywords: clinical cancer research; immunology; lung cancer; metastasis; non-small-cell lung cancer.

MeSH terms

  • B7-H1 Antigen / metabolism
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Lung Neoplasms* / pathology
  • Programmed Cell Death 1 Receptor
  • Retrospective Studies
  • Tumor Burden

Substances

  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor
  • B7-H1 Antigen