Immunotherapy for the First-Line Treatment of Patients with Metastatic Non-Small Cell Lung Cancer

Immunotherapy has fundamentally changed the treatment landscape for many patients with cancer. mAbs targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen-4 immune checkpoints have received regulatory approval across a wide range of tumor types, including non-small cell lung cancer (NSCLC). Indeed, treatment approaches for a majority of patients with newly diagnosed metastatic NSCLC are evolving rapidly. Only for the small proportion of patients with metastatic NSCLC and genomic-driven tumors with EGFR or anaplastic lymphoma kinase (ALK)-sensitizing mutations (5%-15%), and possibly mutations and rearrangements, have initial treatment recommendations remained unchanged, with specific tyrosine kinase inhibitors as the preferred therapy. For the remaining patients, an immunotherapy-based regimen alone or in combination with chemotherapy is now the preferred option based on high-level evidence obtained from randomized controlled trials and in accordance with all available guidelines. Deciding between therapeutic options can be difficult due to the lack of direct cross-comparison studies, differences in chemotherapies and stratification factors, and differences in study populations resulting from inclusion criteria such as histology, PD-L1 expression, or tumor mutational burden (TMB). In an attempt to aid the decision-making process, we discuss and summarize the most recent data from studies using immunotherapies for the treatment of patients with previously untreated metastatic NSCLC.