Efficacy and safety of nivolumab in previously treated patients with non-small cell lung cancer: A multicenter retrospective cohort study

Lung Cancer. 2018 May:119:14-20. doi: 10.1016/j.lungcan.2018.02.017. Epub 2018 Mar 2.

Abstract

Introduction: Nivolumab has been shown to be effective and safe in previously treated patients with advanced non-small cell lung cancer (NSCLC). However, little is known regarding its performance in real-world (i.e., non-trial) settings. Furthermore, nivolumab efficacy is unknown in patients who are ineligible for clinical trials or who are categorized into small subgroups in such trials.

Methods: We conducted a 15-center, observational, retrospective cohort study of patients with advanced NSCLC who received nivolumab monotherapy between January and December 2016.

Results: Of 613 patients included in our study, 141 had poor performance status (PS) and 106 were EGFR mutation - or ALK rearrangement-positive. The response and disease control rates were 20% and 44%, respectively; the estimated 1-year progression-free survival (PFS) was 18%. Multivariate analysis identified never smoking, poor PS, and EGFR mutation/ALK rearrangement as independent negative predictors of PFS. The most frequently reported grade ≥3 adverse event was pneumonitis (5% of patients). Severe pneumonitis (grade ≥3) occurred significantly earlier than mild pneumonitis (1.6 vs. 2.3 months, P = 0.031). Patients with pneumonitis achieved higher response rates and longer PFS than those without (37% vs. 18%, and 5.8 vs. 2.1 months, respectively; P = 0.002).

Conclusions: Smoking status, PS, and EGFR mutation/ALK rearrangement were independent predictors of PFS. Our study elucidated nivolumab's efficacy in previously underreported patient populations; i.e., those with poor PS and/or with driver oncogenes. We also found that pneumonitis is not infrequent, and carries key implications for outcomes. These data should be useful for improving the clinical courses of nivolumab-treated patients with NSCLC.

Keywords: Immune-related adverse event; Nivolumab; Pneumonitis; Programmed cell death 1; Programmed cell death ligand 1.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Aged
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / complications
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Cohort Studies
  • Drug-Related Side Effects and Adverse Reactions / mortality
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Lung Neoplasms / complications
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Nivolumab / therapeutic use*
  • Pneumonia / etiology*
  • Pneumonia / mortality
  • Retrospective Studies
  • Survival Analysis

Substances

  • Antineoplastic Agents, Immunological
  • Nivolumab
  • EGFR protein, human
  • ErbB Receptors