Immune Checkpoint Inhibitor Therapy: What Line of Therapy and How to Choose?

Immunotherapy is now an established part of the treatment paradigm for advanced non-small cell lung cancer (NSCLC), but the line of therapy and the sequence of agents are still in flux. In this time when much is to be learned, the optimal therapy for most patients in both the first-line and previously treated settings is in the context of a clinical trial. For standard therapy, however, there are good data to support the practice of programmed death-ligand 1 (PD-L1) testing in the front-line advanced setting and to use pembrolizumab as first-line therapy for those with ≥50% PD-L1 expression. In those who have progressed after receiving platinum-based chemotherapy in the first-line, multiple PD-1/PD-L1 agents are available and currently approved, including nivolumab, pembrolizumab, and atezolizumab. There are no data to suggest that one agent is more efficacious than the others, but pembrolizumab should be reserved for patients with PD-L1 expression ≥1%. Prescribers and patients must be cognizant of the toxicity profile of these agents, as severe immune-related adverse events can occur with therapy. At this time, this practice pattern for immunotherapy in the first- and second-line can be considered the standard of care, but new data are likely to impact the role of immunotherapy as monotherapy or in combination in the near future.