Treatment Option Overview for NSCLC

In non-small cell lung cancer (NSCLC), results of standard treatment are poor except for the most localized cancers. All newly diagnosed patients with NSCLC are potential candidates for studies evaluating new forms of treatment.

Treatment decisions are based on some of the following factors:

Surgery is potentially the most curative therapeutic option for this disease. Postoperative chemotherapy may provide an additional benefit to patients with resected NSCLC. Radiation therapy combined with chemotherapy can produce a cure in a small number of patients and can provide palliation in most patients. Prophylactic cranial irradiation may reduce the incidence of brain metastases, but there is no evidence of a survival benefit and the effect of prophylactic cranial irradiation on quality of life is not known.[1,2] In patients with advanced-stage disease, chemotherapy or EGFR kinase inhibitors offer modest improvements in median survival, although overall survival is poor.[3,4]

Chemotherapy has produced short-term improvement in disease-related symptoms in patients with advanced NSCLC. Several clinical trials have attempted to assess the impact of chemotherapy on tumor-related symptoms and quality of life. In total, these studies suggest that tumor-related symptoms may be controlled by chemotherapy without adversely affecting overall quality of life;[5,6] however, the impact of chemotherapy on quality of life requires more study. In general, medically eligible older patients with good performance status obtain the same benefits from treatment as younger patients.

The identification of pathogenic variants has led to the development of molecularly targeted therapies for lung cancer that have improved the survival of some patients with metastatic disease.[7] In particular, genetic abnormalities in EGFR, MAPK, and PI3K signaling pathways in subsets of NSCLC may affect drug sensitivity and primary or acquired resistance to kinase inhibitors. EGFR variants strongly predict the improved response rate and progression-free survival in patients who receive EGFR inhibitors. ALK::EML4 fusion genes and other genes form translocation products that occur in 3% to 7% of unselected NSCLC cases and are responsive to pharmacological inhibition of ALK by agents like alectinib. The MET oncogene encodes hepatocyte growth factor receptor. Amplification of this gene has been associated with secondary resistance to EGFR tyrosine kinase inhibitors. Recurrent fusions involving the ROS1 gene are observed in up to 2% of NSCLCs and are responsive to treatment with crizotinib and entrectinib. NTRK gene fusions can occur in up to 1% of NSCLCs and can be treated with the TRK inhibitors, larotrectinib and entrectinib. For more information, see the Molecular Features section.

The treatment options for each stage of NSCLC are presented in Table 5.

In addition to the treatment options presented in Table 5, treatment options under clinical evaluation include: