Diabetes, Metabolic Syndrome and Obesity (Feb 2021)

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

  • Hisanaga K,
  • Uchino H,
  • Kakisu N,
  • Miyagi M,
  • Yoshikawa F,
  • Sato G,
  • Isobe K,
  • Kishi K,
  • Homma S,
  • Hirose T

Journal volume & issue
Vol. Volume 14
pp. 773 – 781

Abstract

Read online

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 [email protected]: 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

Keywords