Clinical Outcomes of Immunotherapy in Stage IV Non-Small Cell Lung Cancer Patients

Abstract

Immunotherapy has revolutionized the treatment landscape for metastatic non-small cell lung cancer (NSCLC), yet therapeutic resistance remains a significant barrier. This study evaluated clinical, molecular, and imaging data from patients treated with immune checkpoint inhibitors (ICIs), including anti-PD-1, anti-PD-L1, and combination regimens. Among the treatment groups, combination immunotherapy demonstrated the highest objective response rate (ORR) at 55% and the longest median overall survival (OS) of 21.3 months. Patients with high PD-L1 expression and elevated tumor mutational burden (TMB) showed superior clinical responses, while resistance was commonly associated with biomarkers such as STK11 loss, T-cell exclusion, and low PD-L1 expression. Immune-related adverse events (irAEs), such as pneumonitis and colitis, occurred in up to 12% of patients, but were generally manageable. Imaging modalities like PET/CT and molecular fluorescence were effective in differentiating pseudo-progression from true progression, improving treatment monitoring. A comprehensive analysis of resistance profiles revealed that 30–50% of patients experienced limited benefit from ICIs due to intrinsic or acquired resistance mechanisms. The study emphasizes the need for biomarker-guided therapy and suggests that integration of immunotherapy with chemotherapy or targeted agents may enhance outcomes. Furthermore, emerging next-generation immunotherapeutics and advanced imaging hold promise for more personalized, adaptive treatment strategies. These findings contribute to the evolving understanding of immunotherapy in NSCLC and support a precision medicine framework to optimize patient management and long-term survival.