PD-1/L1 immune checkpoint inhibitors for KRAS-mutant non-small cell lung cancer: a multicenter retrospective real-world study

Background 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. Methods 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. Their Clinical outcomes and prognostic factors for advanced NSCLC patients with KRAS oncogene mutation were analyzed. Results No significant difference in the objective response rate (ORR) and disease control rate (DCR) was observed between the two groups. The median progression-free survival (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]. Conclusion 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 the neutrophil-to-lymphocyte ratio could serve as markers for predicting the efficacy of immunotherapy in patients with KRAS-mutated NSCLC.