Adjuvant immunotherapy improves survival in completely resected stage IB–III NSCLC: a systematic review and meta-analysis

Abstract

Background: The clinical benefits of postoperative chemotherapy for non-small cell lung cancer (NSCLC) have plateaued, thus highlighting the need for novel strategies. This meta-analysis evaluated the efficacy and safety of adjuvant immunotherapy in patients with completely resected NSCLC and wild-type epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK). Methods: PubMed, Web of Science, Embase, and the Cochrane Library were searched up to February 12, 2025, for studies assessing adjuvant immunotherapy in NSCLC. Primary endpoints included disease-free survival (DFS), overall survival (OS), correlation between subgroup characteristics and efficacy, and safety outcomes, including treatment-related adverse events (TRAEs), severe adverse events (SAEs), and treatment discontinuation. Results: Twelve articles involving 4048 patients were included. Adjuvant immunotherapy significantly improved DFS in patients with resected stage IB–III NSCLC than supportive care or placebo (hazard ratio [HR]: 0.82, 95% confidence interval [CI]: 0.72–0.93, p = 0.01; I2 = 0%, p = 0.46). However, the OS benefit was not significant (HR: 0.9, 95% CI: 0.67–1.21, p = 0.34). DFS benefit was observed in EGFR-negative (HR: 0.75, 95% CI: 0.62–0.91, I2 = 0%), EGFR status unknown (HR: 0.78, 95% CI: 0.63–0.96, I2 = 0%), programmed cell death ligand 1 (PD-L1) 1–49% (HR: 0.75, 95% CI: 0.58–0.97, I2 = 7.13%), non-squamous cell carcinoma (HR: 0.72, 95% CI: 0.61–0.84, I2 = 0%), and never-smoking (HR: 0.68, 95% CI: 0.49–0.96, I2 = 0%) subgroups. The pooled incidences of TRAEs, SAEs, and discontinuation of treatment due to toxicity were 70% (95% CI: 62%–77%), 12% (95% CI: 8%–16%), and 17% (95% CI: 15–19%), respectively. Conclusions: Adjuvant immunotherapy improved DFS in patients with completely resected NSCLC, particularly those who were EGFR-negative, had PD-L1 levels of 1–49%, had non-squamous cell carcinoma, or never smoked. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024547752.