Role of Anti-PD-1 / PD-L1 Immunotherapy in Lung Cancer

Published: Wednesday, Jul 01, 2015
Lung cancer is very common, and patients with advanced-stage and metastatic lung cancer in particular have poor prognoses and greatly reduced quality of life. The main approaches to battling lung cancer have included surgical intervention, chemotherapy, radiation therapy (RT), and certain targeted therapies, but current options may be insufficient for many patients. In recent years, immunotherapy has taken the spotlight as a promising treatment modality, evolving with our increased understanding of the complex relationship between cancer cells and the immune system. The discovery of immune checkpoint proteins and a clearer picture of their role in cancer cell evasion has allowed for specific mobilization of the immune system in new ways. Treatment with monoclonal antibodies (mAbs) that block the inhibitory signals produced by the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway is changing the overall cancer treatment paradigm. This supplement will review the current treatment paradigm for lung cancer and discuss emerging anti–PD-L1 immunotherapies and their clinical data in lung cancer.

Lung Cancer


Lung cancer is one of the most common types of cancer worldwide1 and is the leading cause of cancer death in the United States.1,2 Cancers of the lung and bronchus account for 60.1 new cases of cancer and 48.4 deaths per 100,000 people in the United States each year, based on SEER data from 2007 to 2011. The risk of developing some form of lung or bronchus cancer over the course of a lifetime is about 6.8%, according to 2009-2011 SEER data.3 An estimated 224,210 new cases of lung and bronchus cancer were expected to be diagnosed in 2014, which would account for about 13% of all cancer diagnoses and lead to 159,260 deaths (27.2% of all cancer deaths).3,4 Between 2004 and 2010, the estimated 5-year survival rate of patients with lung cancer was 16.8%. The peak incidence of new cases of lung cancer occurs in patients aged 65 to 74 years, and the median age at diagnosis is 70 years. Men are more likely to develop and die of lung cancer than women.3

Risk Factors

The single most important risk factor for the development of lung cancer is smoking tobacco,2 which is estimated to be responsible for approximately 85% to 90% of all cases of lung cancer.2,5 Smoking increases the risk of developing lung cancer 10- to 20-fold, with the risk further increasing based on both the quantity of cigarettes smoked and the number of years spent smoking.2,6 Secondhand exposure to tobacco smoke also increases the relative risk.2,5

Smoking in combination with exposure to certain occupational or environmental factors compounds the risk of developing lung cancer. In particular, exposure to asbestos (which occurs in automobile shops, shipyards, mines, and textile and cement plants, as well as in construction and insulation workplaces) is thought to combine with smoking to exert a synergistic effect on the risk of lung cancer.2,5,6 Smokers with asbestos exposure have an approximately 50-fold relative risk of lung cancer compared with unexposed nonsmokers.5

Environmental contaminants such as radon, radiation, and air pollution may also increase risk.4 The US Environmental Protection Agency cites radon as the main cause of lung cancer in nonsmokers.7 In addition, lung cancer may occur after exposure to known carcinogens, such as heavy metals (eg, arsenic, beryllium, cadmium, nickel), oxidizing agents (eg, hexavalent chromium), polycyclic aromatic hydrocarbons, and bischloromethyl ether.2,5,6 Occupations associated with increased risk due to chemical exposure include paving, roofing, painting, chimney sweeping, and the manufacture of rubber products.4

Risk is nearly doubled in individuals belonging to families with prior lung cancer,6 potentially due to shared exposure to tobacco smoke and/or environmental carcinogens, or to shared genetic susceptibility (implicated in those who develop the disease at a young age).4,5 Patients with first-degree relatives who have received a lung cancer diagnosis are at 2 to 6 times the risk of patients whose first-degree relatives have not developed lung cancer, even after adjusting for tobacco use.5


The World Health Organization (WHO) divides lung cancer into 2 major classes that have different prognoses and are treated with different strategies2: non-small cell lung cancer (NSCLC), which accounts for the majority (85%) of all lung cancers, and small cell lung cancer (SCLC) (Table 1).2,4-6,8,9 Additionally, there are other neuroendocrine tumors of the lung that are not classified as either NSCLC or SCLC, such as carcinoid and atypical carcinoid tumors.6

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