Efficacy and safety of first-line chemoimmunotherapy versus chemotherapy alone for advanced pulmonary lymphoepithelioma-like carcinoma: a systematic review and real-world cohort study.

BACKGROUND

Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare subtype of non-small cell lung cancer characterized by pronounced regional clustering and high PD-L1 expression. Although early studies suggest that first-line immunotherapy combined with chemotherapy has application potential, we still lack large-sample systematic reviews and cross-high-incidence-area real-world validation.

METHODS

The electronic databases were systematically searched from inception until January 31, 2026. Studies comparing first-line immunotherapy combined with chemotherapy versus chemotherapy alone in patients with advanced primary pulmonary lymphoepithelioma-like carcinoma (PLELC) were included. To validate the findings, an independent multicenter real-world cohort was concurrently incorporated. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Stata 15.0 and R software (utilizing inverse probability of treatment weighting [IPTW]) were used to synthesize the meta-analysis and adjust the real-world cohort data, respectively.

RESULTS

The initial meta-analysis (encompassing 606 patients) demonstrates that adding PD-1/PD-L1 inhibitors to chemotherapy significantly prolongs both progression-free survival (PFS) and overall survival (OS) without elevating the risk of severe adverse events. Within the independent multicenter cohort from Guangxi, the combination therapy group continues to display a profound PFS benefit after IPTW strictly balances the baseline disease burden (18.0 vs. 6.5 months, HR = 0.17, P < 0.001). OS in this cohort exhibits a protective trend (HR = 0.85); however, incorporating this real-world effect size into the global meta-model yields updated pooled data that further reinforces its robust, cross-regional survival advantage (PFS HR = 0.42; OS HR = 0.51). Multivariate prognostic analysis identifies baseline liver metastasis as an independent risk factor for reduced OS, whereas PD-L1 positivity significantly correlates with improved PFS.

CONCLUSION

This integrated systematic review and multicenter real-world cohort study suggests the superior efficacy and safety of first-line chemoimmunotherapy over chemotherapy alone, providing evidence-based support for the management of advanced PPLELC.