Efficacy and safety of sintilimab combined with histology-specific chemotherapy in advanced NSCLC: a real-world retrospective study

Objectives This study aimed to evaluate whether the clinical efficacy of first-line sintilimab combined with histology-specific chemotherapy (adenocarcinoma [ADC]: pemetrexed/platinum [Pem/Plat]; squamous cell carcinoma [SqCC]: paclitaxel/platinum [Pac/Plat]) differs by histological subtype in advanced non-small cell lung cancer (NSCLC). Methods This retrospective, real-world study included 210 patients with advanced NSCLC treated between January 2019 and April 2025 (ADC: n = 124; SqCC: n = 86). The primary endpoints were progression-free survival (PFS) and overall survival (OS). Survival data were analyzed using the Kaplan-Meier method and Cox proportional hazards models, with efficacy heterogeneity tested by incorporating an interaction term. Results In the overall population, sintilimab plus chemotherapy significantly improved both PFS (median PFS: 12.30 vs. 7.30 months, HR = 0.547, P = 0.001) and OS (median OS: 24.30 vs. 17.93 months, HR = 0.647, P = 0.016). Testing for heterogeneity of treatment effect revealed a statistically significant difference in benefit between histological subtypes (PFS interaction P = 0.025; OS interaction P = 0.001). In patients with SqCC, the combination conferred significant PFS (median PFS: 17.17 vs. 6.10 months, HR = 0.382, P = 0.001) and OS benefits (median OS: 52.33 vs. 11.57 months, HR = 0.312, P < 0.001) and emerged as the strongest independent favorable prognostic factor in multivariable analysis. However, in patients with ADC, the combination only showed a trend toward improved PFS (median PFS: 11.53 vs. 8.23 months, HR = 0.641, P = 0.057) and did not lead to a significant OS benefit (median OS: 21.87 vs. 30.50 months, HR = 1.043, P = 0.865). The presence of ≥2 distant metastatic sites was an independent negative prognostic factor in ADC. The safety profile was consistent with the known spectrum of the agents, with no new safety signals identified. Conclusion In real-world practice, the survival benefit of sintilimab combined with histology-specific chemotherapy is significantly dependent on the histological subtype in advanced NSCLC. Patients with SqCC derived a clear and substantial survival advantage, whereas the benefit for patients with ADC was more limited and influenced by high metastatic burden. These findings suggest that in the immunotherapy era, histological subtyping remains a crucial yet insufficient guide for clinical decision-making, and future strategies should integrate subtype-specific biomarkers for further treatment optimization.