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PD-1/L1 immune checkpoint inhibitors for KRAS-mutant non-small cell lung cancer: a multicenter retrospective
Kunchen Wei1, Tiansheng Sun2, Xiao Feng2
1Department of Clinical Laboratory, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China.
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. 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.
Results:
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.
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 NLR could serve as markers for predicting the efficacy of immunotherapy in patients with KRAS-mutated NSCLC.
Insights
First-line immunotherapy with PD-1/L1 immune checkpoint inhibitors (ICIs) demonstrated improved progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) patients with KRAS mutations compared to chemotherapy. Biomarkers like PD-L1 expression can predict treatment efficacy.
Area of Science:
- Oncology
- Immunotherapy
- Genetics
Background:
- KRAS mutations are common in non-small cell lung cancer (NSCLC) and associated with poor prognosis.
- Limited effective treatments exist for advanced NSCLC with KRAS mutations.
Purpose of the Study:
- To evaluate the effectiveness of PD-1/L1 immune checkpoint inhibitors (ICIs) as a first-line treatment for advanced NSCLC patients with KRAS mutations.
Main Methods:
- A multicenter retrospective real-world study (2019-2024) compared 78 patients receiving PD-1/L1 ICIs with 29 patients receiving chemotherapy.
- Primary endpoints included progression-free survival (PFS) and overall survival (OS).
- Secondary endpoints assessed objective response rate (ORR), disease control rate (DCR), and prognostic biomarkers.
Main Results:
- Immunotherapy showed a longer median PFS (7.9 months) than chemotherapy (6.0 months) (P=0.030), with no significant difference in ORR, DCR, or OS.
- PD-L1 expression was an independent protective factor for PFS (P=0.024).
- Elevated C-reactive protein (CRP), CEA, and neutrophil-to-lymphocyte ratio (NLR) were independent risk factors for progression.
Conclusions:
- First-line PD-1/PD-L1 ICIs offer improved PFS in KRAS-mutated NSCLC patients compared to chemotherapy.
- PD-L1 expression, CRP, CEA, and NLR may predict immunotherapy efficacy in this patient population.
