Anti-PD-1/PD-L1 Immunotherapy in Lung Cancer: Update From the ESMO 2016 Congress

Published: Tuesday, Jan 31, 2017

Epidemiology of Lung Cancer

Lung cancer is the leading cause of cancer-related deaths among men and women in the United States, despite being the second most commonly diagnosed cancer.1 Based on Surveillance, Epidemiology, and End Results (SEER) Program data from 2009 to 2013, cancers of the lung and bronchus account for 57.3 new cases of cancer per 100,000 individuals and 46.0 deaths per 100,000 individuals in the United States each year, and the risk of developing some form of lung or bronchus cancer over the course of a lifetime is about 6.5%. Further, in 2016, it was estimated that more than a quarter of all cancer-related deaths (26.5%; 158,000) will be attributed to lung and bronchus cancer.2 Overall, according SEER data, an estimated 224,390 new cases of lung and bronchus cancer will occur in 2016 in the United States, which represents 13.3% of all new cancer diagnoses.2

Targeted Therapies for Lung Cancer

Molecular targeted therapy is a strategy for cancer treatment that relies on exploiting the pathways and mutations that enable tumors to grow and progress. Prior to its introduction, treatment for locally or advanced-stage NSCLC was limited to chemotherapy or radiotherapy.3 Therefore, the introduction of agents that target mechanisms of tumor cell (TC) immune evasion has led to additional options for patients with NSCLC.4 NSCLC TCs exploit the programmed death-1 (PD-1) pathway to evade immune surveillance and destruction through upregulation of suppressive cell surface immune checkpoint regulators, making inhibitors of this pathway an attractive target in NSCLC cancer therapy.3 Many investigators are turning attention toward the identification of additional molecular biomarkers to predict targeted therapeutic efficacy in patients. Currently, programmed death ligand-1 (PD-L1) expression from NSCLC TCs and tumor-infiltrating lymphocytes has been most explored as a predictor of efficacy of anti–PD-1/PD-L1 immunotherapy treatment in clinical trials.

PD-1/PD-L Pathway

In the development of cancer therapies, NSCLC was not traditionally considered to be an immunotherapy-responsive tumor type; however, major responses are well documented in reaction to blockade of the PD-1/PD-L1 pathway with anti-PD-L1 monoclonal antibodies.5
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