Defining aggressive or early progressing nononcogene-addicted non-small-cell lung cancer: a separate disease entity?

Future Oncol. 2019 Apr;15(12):1363-1383. doi: 10.2217/fon-2018-0948. Epub 2019 Feb 13.


A substantial proportion of patients with nononcogene-addicted non-small-cell lung cancer (NSCLC) has 'aggressive disease', as reflected in short time to progression or lack of disease control with initial platinum-based chemotherapy. Recently, clinical correlates of aggressive disease behavior during first-line therapy have been shown to predict greater benefit from addition of nintedanib to second-line docetaxel in adenocarcinoma NSCLC. Positive predictive effects of aggressive disease have since been reported with other anti-angiogenic agents (ramucirumab and bevacizumab), while such features may negatively impact on outcomes with nivolumab in nonsquamous NSCLC with low PD-L1 expression. Based on a review of the clinical data, we recommend aggressive nonsquamous NSCLC should be defined by progression within <6-9 months of first-line treatment initiation.

Keywords: aggressive; anti-angiogenic therapy; non-small-cell lung cancer.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Disease Progression
  • Disease-Free Survival
  • Docetaxel / therapeutic use
  • Humans
  • Indoles / therapeutic use
  • Lung / pathology*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Patient Selection*
  • Time Factors


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Indoles
  • Docetaxel
  • Bevacizumab
  • ramucirumab
  • nintedanib