11 Although cancers derive from a patient’s own tissues, they are characterized by genetic abnormalities that can mark the cancer cells as nonself, triggering an antitumor immune response. 11įor patients whose tumors lack mutations that respond to molecularly targeted therapies, the treatment paradigm has also changed significantly in the past decade with the development of immune checkpoint inhibitors (ICIs), which capitalizes on the potential of the immune response to restrain tumor growth. However, less than 20% of cases are diagnosed at this stage the majority are diagnosed at an advanced stage with distant metastasis and 5-year survival is just 6%.10 Historically, the mainstay of treatment for these patients was platinum-based doublet chemotherapy however, a greater understanding of the molecular pathogenesis of NSCLC facilitated the development of various targeted therapies that have improved survival rates for patients with certain subtypes of metastatic NSCLC. 2įor patients who present with early-stage lung cancer, surgical resection remains the optimal treatment. 8,9 Owing to the implementation of screening guidelines, in addition to efforts to reduce cigarette smoking rates and advancements in treatment, the incidence of lung cancer has been declining since the 1980s among men and since the later part of the 2000s among women. The United States Preventive Services Task Force (USPSTF) recommends annual screening with a chest low-dose computed tomography (CT) scan in high-risk individuals (30 pack-year smoking history) between the ages of 55 and 80 years, unless the individual has not smoked for 15 years or has a limited life span, as this is associated with reduced mortality. 1,6 A number of other risk factors are associated with the development of lung cancer, most notably exposure to radon. 1,5 However, nonsmoking-related lung cancer represents a significant and growing burden, particularly among women and patients younger than 55 years. The most significant risk factor for lung cancer is inhalation of carcinogens from cigarette smoking more than 80% of lung cancer-related deaths are attributed to smoking, with an additional approximately 3% resulting from secondhand smoke exposure. Hispanic individuals have lower lung cancer incidence than non-Hispanics and the lowest annual incidence is observed among Asians/Pacific Islanders. In the United States, the incidence of lung cancer and associated mortality rates is highest among Black men and women compared with other racial and ethnic groups. Lung cancer is more commonly diagnosed in older patients the incidence in individuals under age 40 is low, then gradually increases to a peak between 65 and 84 years of age, with a median age at diagnosis of 71 years. NSCLC is further divided into adenocarcinomas, which account for approximately 40% of cases, squamous cell carcinomas, representing 25% to 30% of cases, and large cell carcinomas comprising 5% to 10%. 1 Although histologically heterogeneous, it can be broadly classified into non−small cell lung cancers (NSCLCs), which make up approximately 85% of cases, and small cell lung cancers. Lung cancer is one of the most common types of cancer and a leading cause of cancer-related death among both sexes in the United States, with 235,760 new cases and 131,880 deaths due to lung cancer anticipated in 2021. This article will evaluate the current and evolving clinical trends in the use of ICIs in the frontline management of metastatic NSCLC, as well as the challenges associated with PD-L1 expression analysis and biomarker implementation.Īm J Manag Care. Presently, PD-L1 expression remains a key biomarker in this setting, in spite of its limitations. With a growing number of FDA-approved ICI monotherapy and combination therapy options for first-line therapy, the use of biomarkers such as PD-L1 expression has become increasingly important in guiding therapeutic decision making. Immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1 (PD-1) receptor and its ligand PD-L1 are an important therapeutic option for patients whose tumors lack genetic alterations that dictate response to molecularly targeted therapies. The frontline treatment paradigm for patients with advanced or metastatic non−small cell lung cancer (NSCLC) has changed dramatically in the past decade amid efforts to tackle this leading cause of cancer-related mortality.
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