Durable Response Following the Discontinuation of Immune Checkpoint Inhibitor Therapy in Advanced Non-small Cell Lung Cancer

Background The optimal duration of immune checkpoint inhibitor (ICI) therapy for maximum benefits remains unclear. Recently, the long-term follow-up data from clinical trials suggest the existence of a durable response (DR) that maintains the therapeutic effect even after ICI discontinuation. The study aimed to explore how the characteristics of ICI therapy influence the effectiveness of subsequent treatments in patients with advanced non-small-cell lung cancer (NSCLC). Methods The medical records of 134 patients with NSCLC who received ICIs before December 31, 2022, were retrospectively reviewed. We evaluated the impact of pretreatment ICIs on survival after completion of ICI administration. Results Among the 116 included patients, long ICI use (≥180 days) was the only independent prognostic factor for post-ICI overall survival (OS) in the multivariate analysis (HR: 0.382, 95% CI: 0.206-0.708, <i>p</i>=0.002). Patients who received ICIs for < 180 days showed significantly improved survival with subsequent chemotherapy (SC) compared to those who received only best supportive care (BSC) (p<0.001). However, among patients treated with ICIs for ≥ 180 days, no significant difference in OS or post-ICI OS was observed between the SC and BSC groups (p=0.188). In patients who discontinued ICIs due to PD, the impact of ICI treatment duration on survival outcomes differed. Among those with short ICI use, the SC group showed significantly better post-ICI OS compared to the BSC group (p=0.007). However, in patients with long ICI use, there was no significant difference in post-ICI OS between the SC and BSC groups (p=0.913). Regarding OS, no statistically significant differences were observed between the SC and BSC groups, regardless of ICI treatment duration. The 2-year OS was 47.6% in the SC group and 46.0% in the BSC group among patients with short ICI use (p=0.549), and 93.3% vs. 66.7% among those with long ICI use (p=0.136). Similarly, in patients who discontinued ICIs without PD, survival outcomes varied depending on ICI duration. Among those with short ICI use, the BSC group had a 2-year post-ICI OS of 21.1%, which was lower than that of the SC group (50.0%; p=0.08). The 2-year OS was also significantly higher in the SC group (64.3%) compared to the BSC group (31.6%; p=0.008). In contrast, no significant differences were observed in post-ICI OS (p=0.104) or OS (64.3% vs. 31.6%; p=0.104) between the SC and BSC groups among patients with long ICI use. Conclusion The achievement of a DR through prolonged ICI use may reduce the need for immediate subsequent chemotherapy in selected patients.