Efficacy and safety of two-year fixed versus continuous immune checkpoint inhibitor therapy in advanced or metastatic non-small cell lung cancer: a systematic review

The optimal duration of immune checkpoint inhibitor (ICI) therapy in advanced or metastatic non-small cell lung cancer (amNSCLC) is unknown. Most trials either continued ICI indefinitely or electively stopped at two years if no progressive disease (PD) or treatment-limiting immune-related adverse events (irAEs) emerged. A systematic review of randomized controlled trials (RCTs) and real-world evidence studies (RWEs) was performed for adults with amNSCLC treated with ICI therapy up to August 24, 2024. Patients were divided into two cohorts: a 2 year fixed cohort in which ICI therapy was discontinued after 2 years and a continuous therapy cohort in which ICI therapy was continued beyond 2 years. Twenty studies and 5027 patients were included. The 5-year overall survival (OS) rates of the two-year fixed cohorts ranged from 69 to 83% across studies and were comparable to continuous therapy cohorts. Four RWEs compared survival outcomes between 2 year fixed and continuous cohorts and found no difference. Patients who completed 2 years of therapy in RCTs tended to have greater rates of irAEs compared to the baseline RCT population. Three RWEs reported higher rates of irAEs in the continuous versus two-year fixed cohorts. Many patients who developed PD after the two-year mark in both cohorts remained alive at the data cutoff. Larger/academic centers favored two-year fixed therapy compared with community centers. Survival outcomes after ICI discontinuation at 2 years are comparable to continuous therapy in amNSCLC. IrAEs tend to accumulate over time.