Efficacy and safety of perioperative, neoadjuvant or adjuvant immunotherapy alone or in combination chemotherapy in early-stage non-small cell lung cancer: A systematic review and meta-analysis of randomized clinical trials.

8025 Background: Adjuvant (AD), neoadjuvant(NE), or perioperative(PE) immunotherapy in early-stage non-small cell lung cancer (eNSCLC) has been validated in multiple clinical trials in recent years. However, the comparations of efficacy and safety among three treatment modalities remain unclear. Methods: The PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) of immune checkpoint inhibitors (ICI) plus chemotherapy (CT) for eNSCLC. We calculated hazard ratios (HRs) or advantage ratios (ORs) for binary endpoints with 95% confidence intervals (CIs). Network meta-analysis was performed using a Bayesian framework to indirectly compare the three treatment modalities. Results: A total of 11 RCTs (2 NE, 6 PE, and 3 AD) including 6951 NSCLC patients were included. Among the three treatment modalities, indirect comparisons revealed that efficacy differed between PE and AD immunotherapy was only observed in the EFS/DFS (HR=0.68, 95%CI: 0.49-0.89). Compared with the control group, NE/PE immunotherapies significantly improved pathologic complete response (pCR) (OR=7.56, 95%CI: 5.24-10.92), major pathologic response(MPR) (OR=5.46, 95%CI: 3.97-7.51), EFS(HR=0.58, 95% CI: 0.50-0.67), and AD immunotherapy significantly improved DFS (HR=0.83, 95% CI: 0.73-0.94). No significant OS difference was observed in NE and AD setting (HR=0.62, 95% CI: 0.36-1.05; HR=0.90, 95% CI: 0.76-1.06, respectively), and only PE immunotherapy showed OS benefits(HR=0.67, 95%CI: 0.54-0.84). In addition, EFS was significantly improved in the PE treatment subgroup regardless of stage, pathologic response, histology, PD-L1 expression, and gender (Table), but no significant benefit in the EGFRm NSCLC subgroup(HR=0.54, 95% CI: 0.21-1.43). AD (OR 1.52, 95% CI: 1.01-2.30) and PE (OR 1.29, 95% CI: 1.08-1.54) immunotherapies were significantly associated with higher grade ≥3 adverse events (AEs) compared with controls. Rash was the most common grade ≥3 irAEs. Conclusions: PE immunotherapy seems to be more effective than NE and AD immunotherapy in three treatment modes. NE and PE immunotherapy significantly improved pCR, MPR, EFS, and AD immunotherapy significantly improved DFS in eNSCLC patients in comparison with the control group, but only PE immunotherapy significantly improved OS. [Table: see text]