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Introduction

Lung cancer is the second most common form of cancer and the leading cause of mortality in the United States. In 2015, an estimated 221,200 new cases were diagnosed, while more than 158,000 lung cancer deaths were reported. The current five-year survival rate, although rising recently, is discouragingly low, 17.4%.¹

Lung cancer is broadly classified into 2 types: non-small–cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). The most common form, NSCLC accounts for about 85% of cases and is divided into 3 histological subtypes based on the cancer cell's biological characteristics and cell of origin: squamous cell carcinoma, large cell carcinoma, and adenocarcinoma.² The recognition that NSCLC is not a single disease entity, but is rather a class of discrete molecularly driven neoplasms, has revised the approach to treatment.³ Alterations in the molecular structure of the tumor have led to the introduction of biological therapies such as erlotinib and crizotinib, which target mutations in proteins such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS1) translocation-driven adenocarcinomas. However, the majority of NSCLC patients' tumors do not express these molecular aberrations; for them, the therapeutic options are more limited. The median overall survival (OS) of patients with metastatic NSCLC is low, about 1 year.⁴ In contrast, SCLC is markedly more aggressive and is associated with rapid tumor progression and early metastasis. Although SCLC is typically responsive to traditional chemotherapy and radiation, relapse is almost universal with advanced disease and the long-term prognosis is poor.⁵

Although immune-based therapies have long been used to treat patients with renal-cell carcinoma and metastatic melanoma, lung cancer has historically been considered to be a low immunogenic disease without a standard immunologic-based treatment. In recent years, a number of novel immunotherapeutic strategies have been evaluated in patients with lung cancer and have been shown to counteract the physiological mechanisms of immune evasion induced by lung-cancer tumors. Essentially, these drugs provoke the immune system to identify and disable tumor-provoked escape routes. Although vaccines and cytokines have shown no benefit to lung cancer patients, a new class of immunotherapy, checkpoint inhibitors, offer a promising approach. This educational activity will explore the therapeutic profile of the first approved immunotherapies, the anti-programmed death-1 (PD-1) antibodies nivolumab and pembrolizumab, in the management of NSCLC. ⁶