Optimal immunotherapy duration in advanced NSCLC: defining the ideal treatment window

Objective: Immune checkpoint inhibitors (ICIs) have demonstrated substantial efficacy in patients with advanced non-small cell lung cancer (NSCLC). However, the optimal duration of ICI therapy remains unclear, and limited real-world data are available. The aim of this study was to evaluate the relationship between ICI therapy duration and overall survival (OS) in patients who achieved varying best overall response (BOR) during ICI treatment, and to compare patients treated for 6 to 18 months vs. at least 18 months. Methods: This retrospective cohort study included adult patients diagnosed with advanced NSCLC who received ICI therapy at the Zhejiang Cancer Hospital between 2017 and 2022. Data collection ended on May 1, 2024, and statistical analysis was performed between May and June 2024. Results: Using strict entry criteria, we screened 487 patients with advanced NSCLC and identified 134 eligible patients. Among these patients, the median durations of immunotherapy and follow-up were 24.57 months and 43.60 months, respectively. The objective response rate (ORR) was 58.2%, and the median progression-free survival (PFS) was 10.6 months. Median OS was not reached. At the last follow-up, 54 patients had no disease progression, and 118 patients remained alive. Patients treated with ICI therapy for ≥ 18 months had superior survival to those treated for 6 to 18 months (P = 0.039). Further analysis revealed that the survival benefit was associated with BOR during ICI therapy. Specifically, patients achieving complete response/partial response (CR/PR) who received ≥ 18 months of ICI therapy had a trend toward longer median OS than those treated for 6 to 18 months, but the difference did not reach statistical significance (P = 0.177). Patients with stable disease (SD) who received ≥ 18 months of ICI therapy had a statistically longer median OS than those treated for 6 to 18 months (P = 0.019). Among patients treated with ICIs for ≥ 18 months, 24 continued with ICI-based therapy and achieved a median PFS2 of 6.67 months, an ORR of 33.3%, and a disease control rate (DCR) of 83.3%. Conclusions: This study provides real-world evidence and novel insights into the need for continuing ICI therapy beyond 18 months in patients with advanced NSCLC who do not exhibit progressive disease. For patients achieving SD during ICI therapy, a treatment duration of at least 18 months appears appropriate. For patients achieving CR/PR, treatment decisions should be individualized according to patient-specific circumstances. However, owing to the retrospective study design, potential selection bias and confounding factors might have influenced the results. Therefore, our findings require further validation in prospective clinical studies.