Over the last year, our world has been consumed by the coronavirus disease 2019 (COVID-19) pandemic. The medical community has dedicated vast amounts of energy and resources toward the viral global crisis, but the incidence of other illnesses is unrelenting.
Although lung cancer is the third most common malignancy in the United States, it accounts for the greatest number of fatalities (FIGURE 1).1 Fortunately, the incidence of new lung cancer cases and deaths has been steadily declining.2
Lung cancer can be attributed to a number of factors that induce cellular malfunction. Smoking is the leading contributor to lung cancer cases throughout the world. The American Lung Association (ALA) reports that up to 90% of occurrences can be attributed to current or former tobacco users, and to patients who were exposed to secondhand smoke.3,4 Environmental carcinogens, such as asbestos, chromium, radon gas, and silica; being 65 years and older; being male; and having a family or prior history of cancer are responsible for initiating malignant cell division5,6 (TABLE 17).
The pathology of lung cancer will guide treatment decisions. Lung cancers can be classified into 2 major groups: non–small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), along with rare variants such as mesothelioma, which accounts for only 5% of all cases but is incurable.8,9
Non–small cell variations are less likely to metastasize due to their slow and delayed development.8 These forms of cancer include adenocarcinomas, squamous cell, and large-cell undifferentiated, which account for up to 80% to 90% of pulmonary neoplasms. Small cell types contribute to 10% to 20% of all lung cancer, which is predominantly related to tobacco smoking.8 SCLCs develop rapidly, metastasize easily, and require immediate intervention due to their aggressive nature.
Lung cancer treatment is a combination of surgery, radiation, and pharmacological therapies. The treatment decision is based on the histology, stage, tumor genetics, and type of cancer. Stages IA and IB of NSCLC can be treated with surgery. Stage II NSCLC requires platinum-doublet chemotherapy and stage III requires a combination of chemotherapy and radiation therapy (TABLE 2).10
The goal of SCLC treatment is to prolong survival. Surgery has a very limited role in treatment and concurrent chemotherapy and radiation therapy are the standard of care (FIGURE 2).10
On the Horizon
Despite representing the highest number of fatalities, lung cancer mortality rates have sharply declined in recent years due to innovative treatment developments and a personalized approach with targeted therapy directed at the genomic profile of individual tumors.
For example, when the EGFR T790M mutation demonstrated resistance to the first-generation EGFR tyrosine-kinase inhibitors erlotinib and gefitinib, osimertinib was developed as a third-generation option. In the FLAURA trial (NCT02296125), osimertinib improved survival by approximately 7 months in patients with untreated, EGFR-mutated advanced NSCLC compared with the first-generation agents (38.6 months [95% CI, 34.5-41.8] in the osimertinib group and 31.8 months [95% CI, 26.6-36.0] in the comparator group; HR for death, 0.8 [0.64-1.00, P = .046]). Due to the study’s crossover nature, the true difference is likely more pronounced, as many patients in the comparator group went on to receive osimertinib once investigators observed the T790M mutation.11
Additionally, advancements have been made in treating rearranged during transfection (RET) fusion–positive NSCLC, which represents 1% to 2% of cases. Results from the LIBRETTO-001 trial (NCT03157128), which analyzed RET-altered lung and thyroid cancers, led to the FDA approval of selpercatinib in May 2020. The NSCLC population was divided into 2 cohorts: patients previously treated with at least platinum-based chemotherapy and those who were previously untreated. In the 105 previously treated patients, 64% (95% CI, 54-73) developed a response, such as decreased tumor size; 63% of responses were ongoing at the median follow-up of 12.1 months. In the 39 patients who were previously untreated, 85% (95% CI, 70-94) responded, with 90% of responses ongoing at 6 months.12
Lung cancer has been described as the poster child of genome-guided precision oncology because of innovations in treatment and the progressive approach to trial design.13 Lung-MAP (NCT02154490) is an ongoing multiple substudy clinical trial focusing on assessing the genomic profiling of squamous tumors in patients with NSCLC. Depending on tumor make-up, patients are either matched to a current substudy testing an investigational drug that best fits their profile or placed in a nonmatched substudy to receive a combination of immunotherapy. The Lung-MAP trial is the first in cancer research to adopt a master protocol model that allows for the incorporation of promising new treatments as the trial progresses.14
Countless improvements have taken place in the management of lung cancer. However, early detection, public education, and smoking cessation remain the most critical components in preventing the disease and enhancing patient survival. Targeted therapy and additional research will continue to advance patient outcomes.