Analysis of survival and prognostic differences in locally advanced or metastatic non-squamous non-small cell lung cancer with KRAS mutations.

Background: Among Eastern populations, the occurrence of Kirsten rat sarcoma viral oncogene (KRAS) mutations in non-small cell lung cancer (NSCLC) is around 10% to 15%. Despite being approved for marketing, targeted drugs are recommended by the Chinese Society of Clinical Oncology (CSCO) Guidelines only as a second-line option, and the selection of first-line treatment regimens remains to be verified. The purpose of this study is to explore the effectiveness of various initial treatment plans for NSCLC with KRAS mutations in real-world settings. Methods: The study reviewed the clinical data of 180 patients with KRAS mutation-positive locally advanced or metastatic non-squamous NSCLC treated at the Chinese People's Liberation Army (PLA) General Hospital over the previous decade. The patients were categorized based on their initial treatment plans to compare therapeutic efficacy and prognosis, and the relevant influencing factors were analyzed. Results: In the 180 patients, median progression-free survival (mPFS) was 8.60 months and median overall survival (mOS) was 17.47 months. Immune checkpoint inhibitors plus chemotherapy (ICIs + CHE) showed the best efficacy, with mPFS 11.30 months, mOS 21.24 months, objective response rate (ORR) 39.29%, and disease control rate (DCR) 89.29%. ICIs included standard programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) antibodies, chemotherapy was platinum-based doublet therapy, and anti-angiogenic therapy was limited to bevacizumab (BEV). This study directly compared ICIs + CHE with the triple combination (ICIs + CHE + BEV) to fill an existing research gap. The ICIs + CHE group had significantly better progression-free survival (PFS) than ICIs or CHE alone, and better overall survival (OS) than CHE alone. Adding anti-angiogenic therapy to ICIs + CHE provided no significant additional benefit. Different level of PD-L1 expression did not affect PFS or OS in immunotherapy-based regimens. In univariate and multivariate analyses, age and gender did not influence PFS; high Eastern Cooperative Oncology Group (ECOG) performance status and bone metastasis were associated with OS. Baseline characteristics were generally comparable across groups, with only minor differences in age, brain metastasis, and PD-L1 expression (P<0.05), which did not independently predict survival. Conclusions: ICIs + CHE is the preferred first-line treatment regimen for patients with locally advanced/metastatic KRAS-mutant non-squamous NSCLC, and the addition of anti-angiogenic agents does not improve therapeutic efficacy. Clinical treatment regimens should be selected individually based on patient characteristics and PD-L1 expression level did not serve as a survival stratification factor for immunotherapy-based treatment regimens.