Current Treatment Options in Oncology

, Volume 15, Issue 4, pp 658–669

Immune Checkpoint Inhibitors in NSCLC

  • Douglas B. Johnson
  • Matthew J. Rioth
  • Leora Horn
Lung Cancer (HA Wakelee, Section Editor)

DOI: 10.1007/s11864-014-0305-5

Cite this article as:
Johnson, D.B., Rioth, M.J. & Horn, L. Curr. Treat. Options in Oncol. (2014) 15: 658. doi:10.1007/s11864-014-0305-5

Opinion statement

Lung cancer is the leading cause of cancer-related mortality worldwide. Cytotoxic chemotherapy and tyrosine kinase inhibitors provide palliation and prolong survival, however, the median survival for patients with metastatic disease remains poor and more effective therapies are needed. Immune checkpoint inhibitors have shown promising results in phase I trials and are being evaluated in ongoing clinical trials in both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients. These include agents targeting the programmed cell death-1 receptor and its ligand (PD-1/PD-L1; notably nivolumab, pembrolizumab, MPDL3280A, and MEDI-4736) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4; ipilimumab and tremelimumab); these agents induce antitumor responses by inhibiting critical negative T cell regulators. In particular, the anti-PD-1/PD-L1 therapies administered as single agent therapy in chemotherapy refractory patients have produced objective response rates ranging from 15 %–25 %, the majority of which were rapid and ongoing 1 year after starting therapy. Furthermore, the toxicity profile for these agents differs from that of cytotoxic chemotherapy but generally is much better tolerated. Promising biomarkers, particularly tumor expression of PD-L1 and tumor infiltrating lymphocytes, may aid in treatment selection and stratification. Ongoing evaluation is needed to define the most appropriate timing and patient population that will benefit from therapy with an immune checkpoint inhibitors and the role of combining these agents with existing therapies including systemic therapy and radiation.

Keywords

Nonsmall cell lung cancer Squamous cell Immune checkpoint inhibitors Checkpoint Immune therapy Ipilimumab 

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Douglas B. Johnson
    • 1
  • Matthew J. Rioth
    • 1
  • Leora Horn
    • 1
  1. 1.Department of Medicine, Division of Hematology/OncologyVanderbilt University Medical Center, Vanderbilt-Ingram Cancer CenterNashvilleUSA