Metastatic squamous cell non-small-cell lung cancer (NSCLC): disrupting the drug treatment paradigm with immunotherapies

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Lung cancer is the third most commonly diagnosed cancer and the leading cause of cancer-related death in the United States. Unlike non-squamous NSCLC, squamous NSCLC rarely harbor epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations for which there are directed therapies, and until the recent approval of immunotherapies for squamous NSCLC, a limited number of traditional cytotoxic chemotherapy drugs have been FDA-approved for use in the treatment of advanced and metastatic squamous NSCLC. Immunotherapies directed at the programmed cell death-1 receptor (PD-1) or its ligand (PD-L1) (nivolumab and pembrolizumab) have demonstrated efficacy in both nonsquamous and squamous cell NSCLC. Because of their similar mechanism of action against the PD-L1/PD-1 pathway, both drugs have similar toxicity profiles related to immune-mediated adverse reactions that can generally be monitored and managed with oral corticosteroids. This paper provides an overview of drug therapy options for squamous cell NSCLC with a focus on the evidence and clinical application of the anti-PD1 therapies. A comparison of the dosing, administration, indications, and differences in the measurement of PD-L1 expression in the clinical trials of nivolumab and pembrolizumab is also provided.

Keywords: carcinoma, squamous cell, carcinoma, non-small-cell lung cancer, immunotherapy, molecular targeted therapy, antibodies, monoclonal, nivolumab, pembrolizumab, cisplatin, carboplatin, gemcitabine, pemetrexed, ramucirumab, bevacizumab, programmed cell death-1 receptor, avelumab, MSB0010718C, MPDL3280A, MEDI4736.

Abbreviations: ALK, anaplastic lymphoma kinase; CNS, central nervous system; EGFR, epidermal growth factor receptor; NSCLC, non-small-cell lung cancer; PD-1, programmed cell death-1 receptor; PD-L1, programmed cell death-1 receptor ligand.

Citation: Scarpace SL. Metastatic squamous cell non-small-cell lung cancer (NSCLC): disrupting the drug treatment paradigm with immunotherapies. Drugs in Context 2015; 4: 212289. DOI: 10.7573/dic.212289

Potential conflicts of interests: The International Committee of Medical Journal Editors’ (ICMJE) Potential Conflicts of Interests form for the author is available for download at: The author has no relationships to disclose.

Funding declaration and acknowledgment: The author has declared that this is an unfunded review.

Copyright: Copyright © 2015 Scarpace SL. Distributed under the terms of the Creative Commons License Deed CC BY NC ND 3.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2015 Scarpace SL. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 3.0.

Article URL: -paradigm-with-immunotherapies

Correspondence: Sarah L Scarpace, Albany College of Pharmacy and Health Sciences, Albany, NY 12208, USA; St. Peter’s Health Partners Cancer Care Center, Albany, NY, USA.

Provenance: Submitted, externally peer reviewed

Submitted: 15 September 2015; Peer review comments to author: 28 September 2015; Publication date: 14 October 2015

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