Strategies to optimize duration of immunotherapy in advanced NSCLC: Current evidence and future directions

Immune checkpoint inhibitors have revolutionized the treatment of advanced non-small cell lung cancer, yet the optimal duration of therapy remains uncertain, raising concerns about cumulative toxicity, economic burden, and potential overtreatment. We analyzed the current evidence comparing fixed-duration regimens (typically capped at 2 years) with continuous treatment until disease progression or unacceptable toxicity, focusing on their impact on long-term survival, disease control, and adverse event risks. Biomarkers, particularly circulating tumor DNA kinetics, play a critical role in guiding individualized treatment duration, providing greater precision in monitoring disease response and tailoring therapy. Additionally, we discuss different approaches for managing patients after treatment discontinuation, such as rechallenging following immune-related adverse events (irAEs).This review summarizes the current evidence on fixed versus indefinite immunotherapy duration and proposes a biomarker-informed, patient-centered framework for optimizing immunotherapy duration, aiming to balance therapeutic efficacy and minimize toxicity.