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

• Published in: Anticancer research 2021-04, Vol.41 (4), p.2093-2100
• Main Authors: Tozuka, Takehiro, Yanagitani, Noriko, Yoshida, Hiroshi, Manabe, Ryo, Ogusu, Shinsuke, Tsugitomi, Ryosuke, Sakamoto, Hiroaki, Amino, Yoshiaki, Ariyasu, Ryo, Uchibori, Ken, Kitazono, Satoru, Seike, Masahiro, Gemma, Akihiko, Nishio, Makoto
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Angiotensin; Angiotensin Receptor Antagonists - pharmacology; Angiotensin Receptor Antagonists - therapeutic use; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antibodies; Antibodies, Monoclonal, Humanized - therapeutic use; Antihypertensive Agents - therapeutic use; Antineoplastic Agents, Immunological - administration & dosage; Antineoplastic Agents, Immunological - therapeutic use; Apoptosis; 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; Cell death; Drug Synergism; Female; Humans; Hypertension - complications; Hypertension - drug therapy; Hypertension - epidemiology; Immunosuppression; Inhibitors; Japan - epidemiology; Lung cancer; Lung Neoplasms - complications; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Middle Aged; Nivolumab - therapeutic use; Non-small cell lung carcinoma; PD-1 protein; PD-L1 protein; Renin; Renin-Angiotensin System - drug effects; Retrospective Studies; Small cell lung carcinoma; Survival Analysis; Treatment Outcome; Tumor microenvironment; Tumors
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.14980

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. 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. 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). 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.