Consolidated PD-L1 inhibitors after chemoradiotherapy versus placebo in non-resectable non–small cell lung carcinoma: A meta-analysis of phase III randomized controlled trials.

Abstract

e20075 Background: The PACIFIC trial established the use of durvalumab, an immune-checkpoint inhibitor (ICI), following concurrent chemoradiotherapy in the treatment of non-small cell lung carcinoma. However, the safety and efficacy of PD-L1 inhibitors besides durvalumab has not been adequately explored, and the comparative efficacy of concurrent vs sequential chemoradiotherapy (CRT) in combination with immune checkpoint blockade remains questionable. Additionally, pneumonitis, the most frequently reported immune-related adverse event, has not been systematically analyzed across different immunotherapeutic agents. There remains a dearth of pooled evidence from randomized controlled trials (RCTs) providing definitive evidence in the literature. Methods: We systematically searched PubMed, Embase, Scopus, and Cochrane from inception to January 2026. Heterogeneity was assessed using I 2 statistics. Random-effects models were used to calculate pooled proportions and risk ratios (RR) for survival and toxicity outcomes with 95% confidence intervals. Results: Out of 2,287 articles screened, 4 articles were included. We found that the ICI group had a 13% lower risk of disease progression or death compared to the placebo group although the result was statistically insignificant (p = 0.12, I 2 = 0). Durvalumab achieved greater overall survival at 1 year (RR = 1.15, p = 0.03, I 2 = 32%), 2 years (RR = 1.17, p = 0.005, I 2 = 0%) and progression free survival at 1 year (RR = 1.16, p = 0.02, I 2 = 0%) compared to placebo. However, subgroup analysis revealed no statistically significant difference in terms of survival for concurrent and sequential chemoradiotherapy. Grade 3+ toxicity was reported to be consistently higher in PD-L1 inhibitors group compared to placebo group (RR = 1.33, p = 0.002, I 2 = 70%), with pneumonitis being the most common reaction (RR = 2.97, p = 0.0005, I 2 = 0%). PD-L1 inhibitors significantly increased the risk of pneumonitis compared with placebo (overall RR = 2.97), with durvalumab showing a lower risk than other PD-L1 inhibitors (RR = 2.68 vs 4.84). However, while such an indirect comparison suggests durvalumab may have a lower risk of pneumonitis compared to other PD-L1 inhibitors, such a result must be interpreted cautiously. Conclusions: ICIs demonstrate improved overall and progression-free survival compared to placebo, but increase the risk of severe toxicity, particularly pneumonitis. Durvalumab may confer a lower risk of pneumonitis compared to other PD-L1 inhibitors. Concurrent and sequential CRT show comparable efficacy.