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

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.