Efficacy and safety of immune checkpoint inhibitor rechallenge in non‐small cell lung cancer: A systematic review and meta‐analysis

BACKGROUND: The aim of the study was to explore the efficacy and safety of immune checkpoint inhibitor (ICI) rechallenge in patients with non‐small cell lung cancer (NSCLC). METHODS: Studies that enrolled NSCLC patients treated with two lines of ICIs were included using four databases. The initial line (1L‐) and subsequent lines (2L‐) of ICIs were defined as 1L‐ICI and 2L‐ICI, respectively. RESULTS: A total of 17 studies involving 2100 patients were included. The pooled objective response rate (ORR), disease control rate (DCR), median progression‐free survival (mPFS), and median overall survival (mOS) for 2L‐ICIs were 10%, 50%, 3.0 months, and 13.1 months, respectively. The 2L‐ICI discontinuation rates caused by toxicities ranged from 0% to 23.5%. Original data were extracted from six studies, covering 89 patients. Patients in whom 1L‐ICIs were discontinued following clinical decision (the mPFS of 2L‐ICIs was not reach) achieved a more prolonged mPFS of 2L‐ICIs than those due to toxicity (5.2 months) and progressive disease (2.1 months) (p < 0.0001). Patients' 1L‐PFS for more than 2‐years had preferable 2L‐ORR (35.0% vs. 9.8%, p = 0.03), 2L‐DCR (85.0% vs. 49.0%, p = 0.007), and 2L‐mPFS (12.4 vs. 3.0 months, p < 0.0001) than those less than 1‐year. Patients administered the same drugs achieved a significantly prolonged mPFS compared with the remaining patients (5.4 vs. 2.3 months, p = 0.0004), and those who did not accept antitumor treatments during the intervals of two lines of ICIs achieved a prolonged mPFS compared to those patients who did accept treatments (7.6 vs. 1.9 months, p < 0.0001). CONCLUSIONS: ICI rechallenge is a useful therapeutic strategy for NSCLC patients, especially suitable for those who achieve long‐term tumor remission for more than 2‐years under 1L‐ICIs.