Analysis of Early Death in Japanese Patients With Advanced Non-small-cell Lung Cancer Treated With Nivolumab

Clin Lung Cancer. 2018 Mar;19(2):e171-e176. doi: 10.1016/j.cllc.2017.09.002. Epub 2017 Oct 13.

Abstract

Background: The increased risk for early death owing to anti-programmed cell death 1 inhibitors is a major disadvantage that requires special management. We evaluated the frequency, causes, and risk factors of early death during nivolumab treatment for non-small cell lung cancer (NSCLC) in a Japanese clinical setting.

Patients and methods: The medical records of patients with NSCLC who started receiving nivolumab between December 17, 2015 and July 31, 2016 in 3 Japanese institutes were collected. Early death was defined as any death within 3 months from the start of nivolumab treatment, irrespective of its cause. Treatment response was evaluated using the Response Evaluation Criteria In Solid Tumors criteria, version 1.1.

Results: A total of 201 patients with NSCLC were enrolled, and 38 (18.9%) died within the first 3 months. Thirty-one (81.6%) patients who experienced early death developed progressive disease, whereas 14 (36.8%) patients who experienced early death demonstrated nivolumab-induced immune-related adverse events, which required corticosteroid intervention, including interstitial lung disease in 7 (18.4%) patients. Multivariate logistic regression demonstrated that an Eastern Cooperative Oncology Group performance status score ≥ 2 (odds ratio [OR], 5.66; 95% confidence interval [CI], 2.01-15.61; P < .001), C-reactive protein-to-albumin ratio > 0.3 (OR, 10.56; 95% CI, 3.61-30.86; P < .001), and the response to prior treatment (OR, 2.07; 95% CI, 1.03-4.14; P = .041) were independent predictors for early death.

Conclusion: Disease progression and immune-related adverse events are 2 major causes of early death with nivolumab in patients with NSCLC. An Eastern Cooperative Oncology Group performance status score ≥ 2, pretreatment C-reactive protein-to-albumin ratio > 0.3, and poor response to prior treatment were associated with early death.

Keywords: C-reactive protein albumin ratio; Early mortality; Immune-checkpoint inhibitor; Non–small-cell lung cancer; Risk factor.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / epidemiology*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Drug-Related Side Effects and Adverse Reactions / mortality
  • Female
  • Humans
  • Immune System Diseases / epidemiology*
  • Immune System Diseases / etiology
  • Immune System Diseases / mortality
  • Immunotherapy / adverse effects*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / epidemiology*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Mortality, Premature
  • Nivolumab / adverse effects*
  • Nivolumab / therapeutic use
  • Programmed Cell Death 1 Receptor / immunology
  • Risk
  • Survival Analysis

Substances

  • Antineoplastic Agents
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab