Impact of Renin-angiotensin System Inhibitors on the Efficacy of Anti-PD-1/PD-L1 Antibodies in NSCLC Patients

Anticancer Res. 2021 Apr;41(4):2093-2100. doi: 10.21873/anticanres.14980.

Abstract

Background/aim: The Renin-Angiotensin system (RAS) induces immunosuppression in the tumor microenvironment, and RAS inhibitors (RASi) improve the tumor immune microenvironment. We evaluated the impact of RASi on the efficacy anti-programmed cell death-1/Ligand-1 (anti-PD-1/PD-L1) antibodies.

Patients and methods: This retrospective study analyzed non-small cell lung cancer (NSCLC) patients who received anti-PD-1/PD-L1 antibodies monotherapy as second- or later-line treatment. We classified patients into those with or without use of RASi.

Results: A total of 256 NSCLC patients were included and 37 patients used RASi. The median PFS of patients treated with RASi was significantly longer than that of patients treated without (HR=0.59, 95%CI=0.40-0.88). The median OS of patients treated with RASi tended to be longer than that of patients treated without (HR=0.71, 95%CI=0.45-1.11).

Conclusion: The use of RASi was associated with a significantly longer PFS in NSCLC patients treated with anti-PD-1/PD-L1 antibodies. RASi use may enhance the efficacy of anti-PD-1/PD-L1 antibodies.

Keywords: Renin–angiotensin system inhibitors; anti-programmed cell death 1/ligand-1 antibodies; immunotherapy; non-small cell lung cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin Receptor Antagonists / pharmacology*
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antihypertensive Agents / therapeutic use
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B7-H1 Antigen / immunology
  • Carcinoma, Non-Small-Cell Lung / complications
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Drug Synergism
  • Female
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy
  • Hypertension / epidemiology
  • Japan / epidemiology
  • Lung Neoplasms / complications
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Nivolumab / therapeutic use
  • Renin-Angiotensin System / drug effects
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Antihypertensive Agents
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • CD274 protein, human
  • Nivolumab
  • atezolizumab
  • pembrolizumab