Combination immunotherapy strategies in advanced non-small cell lung cancer (NSCLC): Does biological rationale meet clinical needs?

Crit Rev Oncol Hematol. 2017 Nov:119:30-39. doi: 10.1016/j.critrevonc.2017.09.007. Epub 2017 Sep 19.

Abstract

Immune checkpoint inhibitors (ICIs) have emerged as one of the main new therapeutic options for advanced non-small cell lung cancer (NSCLC) patients. Even though they demonstrated superiority towards standard chemotherapy in different disease settings, the response rates do not exceed 45% in highly molecularly selected patients. This is related to known limitations of the available biomarkers, as well to the complex and dynamic nature of tumor microenvironment. The study of the different strategies adopted by tumor cells to escape the immune system lays the basis of the new combination strategies. This review focuses on analyzing the biological rationale and early clinical data available concerning therapeutic strategies combining ICIs together, ICIs with different regimens and schedules of standard chemotherapy, ICIs with tyrosine kinase inhibitors, ICIs with antiangiogenic agents and ICs with radiotherapy.

Keywords: Antiangiogenic treatment; CTLA-4; Combination treatment; IDO; Immune checkpoint; LAG-3; Lung cancer; PD-L1.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / immunology
  • CTLA-4 Antigen / antagonists & inhibitors
  • CTLA-4 Antigen / immunology
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Humans
  • Immunotherapy / methods
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / therapy*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology
  • Tumor Escape

Substances

  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • CTLA-4 Antigen
  • Programmed Cell Death 1 Receptor