KRAS (Kirsten rat sarcoma viral oncogene homolog) gene mutation is one of the common driver gene mutations in non-small cell lung cancer (NSCLC) with poor prognosis. There are limited effective treatments for advanced NSCLC patients with KRAS mutation. This study aimed to evaluate the effectiveness of PD-1/L1 immune checkpoint inhibitors (ICIs) as a first-line immunotherapy for advanced NSCLC patients harboring KRAS oncogene mutation.

This multicenter retrospective real-world study was conducted from 2019 to 2024 at Shanghai Changzheng Hospital and Shanghai Municipal Hospital of Traditional Chinese Medicine, including 78 patients who received immunotherapy using PD-1/L1 ICIs, and 29 patients who received traditional platinum-doublet chemotherapy. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints included the objective response rate (ORR), disease control rate (DCR), and correlation of prognostic biomarkers with survival outcomes.

No significant difference in ORR and DCR was observed between the two groups. The median PFS in immunotherapy group was longer than that in chemotherapy group [7.9 months (95% CI: 5.3–10.5) vs. 6.0 months (95% CI: 3.8–8.2), P = 0.030], and there was no significant difference in OS between the two groups (16.2 vs. 19.2 months, P > 0.05). Multivariate analysis identified PD-L1 expression as an independent protective factor for PFS (HR = 0.397, 95% CI: 0.178–0.887, P = 0.024), and elevated CRP (HR = 1.005, 95% CI: 1.001–1.010, P = 0.022), CEA (HR = 1.008, 95% CI: 1.001–1.014, P = 0.030) and neutrophil-to-lymphocyte ratio (NLR) (HR = 1.105, 95% CI: 1.024–1.193, P = 0.010) were independent risk factors for progression.

The first-line treatment with PD-1/PD-L1 ICIs showed numerically better clinical efficacy than the traditional double-agent chemotherapy in patients with KRAS-mutated NSCLC, especially in PFS. Additionally, PD-L1 expression, C reactive protein, CEA, and NLR could serve as markers for predicting the efficacy of immunotherapy in patients with KRAS-mutated NSCLC.