Pre-Existing Diabetes Limits Survival Rate After Immune Checkpoint Inhibitor Treatment for Advanced Lung Cancer: A Retrospective Study in Japan

Kaori Hisanaga,1 Hiroshi Uchino,1 Naoko Kakisu,1 Masahiko Miyagi,1 Fukumi Yoshikawa,1 Genki Sato,1 Kazutoshi Isobe,2 Kazuma Kishi,2 Sakae Homma,3 Takahisa Hirose1 1Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, Tokyo, Japan; 2...

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Autores principales:	Hisanaga K, Uchino H, Kakisu N, Miyagi M, Yoshikawa F, Sato G, Isobe K, Kishi K, Homma S, Hirose T
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	immune checkpoint inhibitor diabetes overall survival progression-free survival Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/52599842f7d840b0a9eb73a2c5b94373
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spelling	oai:doaj.org-article:52599842f7d840b0a9eb73a2c5b943732021-12-02T10:59:35ZPre-Existing Diabetes Limits Survival Rate After Immune Checkpoint Inhibitor Treatment for Advanced Lung Cancer: A Retrospective Study in Japan1178-7007https://doaj.org/article/52599842f7d840b0a9eb73a2c5b943732021-02-01T00:00:00Zhttps://www.dovepress.com/pre-existing-diabetes-limits-survival-rate-after-immune-checkpoint-inh-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Kaori Hisanaga,1 Hiroshi Uchino,1 Naoko Kakisu,1 Masahiko Miyagi,1 Fukumi Yoshikawa,1 Genki Sato,1 Kazutoshi Isobe,2 Kazuma Kishi,2 Sakae Homma,3 Takahisa Hirose1 1Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, Tokyo, Japan; 2Department of Respiratory Medicine, Toho University Graduate School of Medicine, Tokyo, Japan; 3Department of Advanced and Integrated Interstitial Lung Disease Research, School of Medicine, Toho University, Tokyo, JapanCorrespondence: Hiroshi UchinoDivision of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, 6-11-1 Omori-Nishi, Ota-Ku, Tokyo, 143-8541, JapanTel +81-3-3762-4151Fax +81-3-3765-6488Email h.uchino@med.toho-u.ac.jpBackground: Although immune checkpoint inhibitors (ICIs) are promising in the treatment of advanced cancer, their use is associated with immune-related adverse events (irAEs) that affect endocrine organ systems. Although development of irAEs was associated with improved cancer-specific survival, the risk of irAEs is unclear. We investigated the association of pre-ICI comorbidities—including diabetes—with irAEs, overall survival (OS), and progression-free survival (PFS) in advanced lung cancer.Methods: Patients with lung cancer who were treated with ICIs during the period from September 1, 2015 through July 31, 2018 were retrospectively enrolled. All data were collected from the NEPTUNE database of university patients. Hazard ratios were estimated by using Cox regression weighted for propensity scores. Odds ratios were calculated by logistic regression and adjusted for unbalanced variables. The Kaplan–Meier method was used to compare OS, and the generalized Wilcoxon test was used to compare median survival.Results: Among the 88 patients identified, 22 (25.0%) had diabetes (DM) before ICI treatment and 57 (75.0%) did not (non-DM); irAEs developed in 12.2% of patients with DM and in 9.1% of patients in non-DM (p=0.87). Diabetes status was not associated with irAE risk in relation to baseline characteristics (age, sex, TNM staging, thyroid and renal function) or in propensity score–matched analysis (age, TNM staging). During a mean follow-up of 30 months, OS and cancer-specific PFS were significantly higher in patients who developed irAEs (Kaplan–Meier estimates, p=0· 04 and 0· 03, respectively). In propensity score–matched analysis, diabetes was significantly associated with lower OS (multivariate hazard ratio, 0· 36; 95% CI, 0· 13– 0· 98) unrelated to irAEs. Irrespective of irAEs, PFS was also lower among patients with DM than among non-DM patients (Kaplan–Meier estimate, p=0· 04).Conclusion: Pre-existing diabetes was associated with higher mortality in advanced lung cancer, regardless of irAE development during treatment with ICI.Keywords: immune checkpoint inhibitor, diabetes, overall survival, progression-free survivalHisanaga KUchino HKakisu NMiyagi MYoshikawa FSato GIsobe KKishi KHomma SHirose TDove Medical Pressarticleimmune checkpoint inhibitordiabetesoverall survivalprogression-free survivalSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 773-781 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	immune checkpoint inhibitor diabetes overall survival progression-free survival Specialties of internal medicine RC581-951
spellingShingle	immune checkpoint inhibitor diabetes overall survival progression-free survival Specialties of internal medicine RC581-951 Hisanaga K Uchino H Kakisu N Miyagi M Yoshikawa F Sato G Isobe K Kishi K Homma S Hirose T Pre-Existing Diabetes Limits Survival Rate After Immune Checkpoint Inhibitor Treatment for Advanced Lung Cancer: A Retrospective Study in Japan
description	Kaori Hisanaga,1 Hiroshi Uchino,1 Naoko Kakisu,1 Masahiko Miyagi,1 Fukumi Yoshikawa,1 Genki Sato,1 Kazutoshi Isobe,2 Kazuma Kishi,2 Sakae Homma,3 Takahisa Hirose1 1Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, Tokyo, Japan; 2Department of Respiratory Medicine, Toho University Graduate School of Medicine, Tokyo, Japan; 3Department of Advanced and Integrated Interstitial Lung Disease Research, School of Medicine, Toho University, Tokyo, JapanCorrespondence: Hiroshi UchinoDivision of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, 6-11-1 Omori-Nishi, Ota-Ku, Tokyo, 143-8541, JapanTel +81-3-3762-4151Fax +81-3-3765-6488Email h.uchino@med.toho-u.ac.jpBackground: Although immune checkpoint inhibitors (ICIs) are promising in the treatment of advanced cancer, their use is associated with immune-related adverse events (irAEs) that affect endocrine organ systems. Although development of irAEs was associated with improved cancer-specific survival, the risk of irAEs is unclear. We investigated the association of pre-ICI comorbidities—including diabetes—with irAEs, overall survival (OS), and progression-free survival (PFS) in advanced lung cancer.Methods: Patients with lung cancer who were treated with ICIs during the period from September 1, 2015 through July 31, 2018 were retrospectively enrolled. All data were collected from the NEPTUNE database of university patients. Hazard ratios were estimated by using Cox regression weighted for propensity scores. Odds ratios were calculated by logistic regression and adjusted for unbalanced variables. The Kaplan–Meier method was used to compare OS, and the generalized Wilcoxon test was used to compare median survival.Results: Among the 88 patients identified, 22 (25.0%) had diabetes (DM) before ICI treatment and 57 (75.0%) did not (non-DM); irAEs developed in 12.2% of patients with DM and in 9.1% of patients in non-DM (p=0.87). Diabetes status was not associated with irAE risk in relation to baseline characteristics (age, sex, TNM staging, thyroid and renal function) or in propensity score–matched analysis (age, TNM staging). During a mean follow-up of 30 months, OS and cancer-specific PFS were significantly higher in patients who developed irAEs (Kaplan–Meier estimates, p=0· 04 and 0· 03, respectively). In propensity score–matched analysis, diabetes was significantly associated with lower OS (multivariate hazard ratio, 0· 36; 95% CI, 0· 13– 0· 98) unrelated to irAEs. Irrespective of irAEs, PFS was also lower among patients with DM than among non-DM patients (Kaplan–Meier estimate, p=0· 04).Conclusion: Pre-existing diabetes was associated with higher mortality in advanced lung cancer, regardless of irAE development during treatment with ICI.Keywords: immune checkpoint inhibitor, diabetes, overall survival, progression-free survival
format	article
author	Hisanaga K Uchino H Kakisu N Miyagi M Yoshikawa F Sato G Isobe K Kishi K Homma S Hirose T
author_facet	Hisanaga K Uchino H Kakisu N Miyagi M Yoshikawa F Sato G Isobe K Kishi K Homma S Hirose T
author_sort	Hisanaga K
title	Pre-Existing Diabetes Limits Survival Rate After Immune Checkpoint Inhibitor Treatment for Advanced Lung Cancer: A Retrospective Study in Japan
title_short	Pre-Existing Diabetes Limits Survival Rate After Immune Checkpoint Inhibitor Treatment for Advanced Lung Cancer: A Retrospective Study in Japan
title_full	Pre-Existing Diabetes Limits Survival Rate After Immune Checkpoint Inhibitor Treatment for Advanced Lung Cancer: A Retrospective Study in Japan
title_fullStr	Pre-Existing Diabetes Limits Survival Rate After Immune Checkpoint Inhibitor Treatment for Advanced Lung Cancer: A Retrospective Study in Japan
title_full_unstemmed	Pre-Existing Diabetes Limits Survival Rate After Immune Checkpoint Inhibitor Treatment for Advanced Lung Cancer: A Retrospective Study in Japan
title_sort	pre-existing diabetes limits survival rate after immune checkpoint inhibitor treatment for advanced lung cancer: a retrospective study in japan
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/52599842f7d840b0a9eb73a2c5b94373
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Pre-Existing Diabetes Limits Survival Rate After Immune Checkpoint Inhibitor Treatment for Advanced Lung Cancer: A Retrospective Study in Japan

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