Risk factors for immunoresistance in advanced non-small cell lung cancer and the advantages of targeted therapy in improving prognosis

Abstract

Objectives: The advent of immunotherapy has transformed the therapeutic landscape for advanced non- small cell lung cancer (NSCLC); nonetheless, the emergence of resistance to immunotherapy poses a considerable obstacle. Our research sought to identify factors contributing to immunotherapy resistance and to assess the effectiveness of subsequenttreatments in patients with advanced NSCLC who have been exposed to immune checkpoint inhibitors (ICIs). Methods: This retrospective study analyzed data from 232 individuals with advanced NSCLC who were treated with ICIs duringJanuary 2020 to December 2023. Based on their response to ICIs, these patients were classified into two groups: immunoresistance group (IM group) and non-immunoresistance group (NIM group). Data collected included demographics, clinical parameters, cytokine profiles, tumor mutational burden (TMB), PD-L1 expression, overall survival (OS), progression-free survival (PFS), and adverse events. The association between risk factors and immunoresistance were assessed, and second-line treatment outcomes were evaluated. Results: Key risk factors for immunoresistance included lower TMB, higher levels of interleukin-10 (IL-10), and PD-L1 expression = 50%. TMB was inversely correlated with immunoresistance (rho =-0.838, P 0.001). In multivariate analysis, IL-10 remained a significant risk factor (OR = 33.654, P = 0.021), whereas TMB was protective (OR = 0.786, P 0.001). Second-line targeted therapy significantly improved OS (8.72 +/- 2.02 months) and PFS (5.37 +/- 2.15 months) compared to chemotherapy (OS: 7.93 +/- 2.13 months; PFS: 4.86 +/- 1.68 months) (P 0.05). The targeted therapy group experienced distinct side effects, notably increased hypertension and hand-foot syndrome, while chemotherapy group had higher rates of fatigue (P 0.05). Conclusion: Immunoresistance in advanced NSCLC is influenced by IL-10, TMB, and PD-L1 expression. Targeted therapies offer superior outcomes than chemotherapy, though side effect management remains crucial.