Efficacy of immunotherapy as second-line or later-line therapy and prognostic significance of KRAS or TP53 mutations in advanced non-small cell lung cancer patients

Abstract

Objective In this retrospective study, we aimed to assess the relationship between mutations in the Kirsten rats sarcoma viral oncogene (KRAS)/ tumor protein p53 (TP53) genes and the efficacy of immune checkpoint inhibitors (ICIs) therapy as a second-line or later-line treatment for patients with stage IIIB/IV non-small cell lung cancer (NSCLC). Methods We retrospectively analyzed the clinical data of 143 patients with stage IIIB/IV NSCLC who were admitted to the Cancer Hospital of Harbin Medical University between January 2019 and September 2022. Kaplan–Meier survival curve analysis was performed to analyze the survival outcomes. Univariate and multivariate Cox proportional risk models were used to analyze the factors associated with the progression-free survival (PFS) and overall survival (OS) of advanced-stage NSCLC patients who received ICIs as second-line or later-line therapy. Results NSCLC patients with KRAS or TP53 mutations treated with ICIs showed significantly higher objective response rate, disease control rate, PFS, and OS compared to NSCLC patients with wild-type KRAS/TP53 (P < 0.05). Multivariate Cox regression analysis showed that a combined treatment regimen of ICIs plus chemotherapy was significantly associated with prolonged PFS [hazard ratio = 0.192; 95% confidence interval (CI), 0.094–0.392; P < 0.001] and OS (hazard ratio = 0.414; 95% CI, 0.281–0.612; P < 0.001). Conclusion KRAS or TP53 mutations were associated with improved PFS of advanced NSCLC patients treated with ICIs as second-line or later-line therapy. KRAS or TP53 mutations show great potential as clinical biomarkers to predict the efficacy of ICIs therapy.