Real-World Outcomes and Clinical Predictors of Immune Checkpoint Inhibitor Monotherapy in Advanced Lung Cancer

Abstract

Background: Immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of advanced-stage non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). The aim of this study was to evaluate the effectiveness and tolerance of ICIs in a real-world patient population and to investigate the predictive factors associated with survival outcomes. Methods: Medical records of patients with advanced lung cancer who started ICI monotherapy were reviewed for data collection. Treatment outcomes included objective response rate, progression-free survival (PFS), and overall survival (OS). Immune-related adverse events (irAEs) were assessed. Multiple Cox regression models were fit to investigate the predictive factors for survival outcomes. Results: We included 220 patients (median 66.5 years). Seventy-nine (35.9%) patients had Eastern Cooperative Oncology Group (ECOG) performance-status (PS) score ⩾2. Median follow-up was 11.4 months. In NSCLC, median PFS was 3.8 months (4.7 months for first line and 3.7 months for subsequent line). Median OS was 12.4 months (15.6 months for first line therapy and 11.5 months for subsequent line). In SCLC, median PFS was 1.8 months, and median OS was 4.6 months. A quarter of patients developed irAEs. There was 1 disease flare among 17 patients with pre-existing autoimmune diseases. ECOG PS of 0 to 1 and body mass index (BMI) ⩾ 25 kg/m2 (but not occurrence of irAE) were independently associated with improved OS in NSCLC, with a hazard ratio of 0.41 (95% confidence interval [CI], 0.29-0.59) and 0.62 (95% CI, 0.44-0.87), respectively. Conclusions: The clinical benefit of ICIs appears to persist in a real-world population of relatively older age, including those with poor PS and pre-existing autoimmune diseases. ECOG PS of 0 to 1 and BMI ⩾ 25 kg/m2 were independently associated with improved OS.

Real-World Outcomes and Treatments Patterns Prior and after the Introduction of First-Line Immunotherapy for the Treatment of Metastatic Non-Small Cell Lung Cancer

“…Survival estimates were generally shorter than those reported in previous real-world studies for both cohorts [ 20 , 21 , 22 , 23 , 24 , 25 ]. There are possibly some underlying EGFR/ALK/ROS1-positive patients, as not all patients were tested for underlying mutations/aberrations.…”

Immunotherapy as Novel Treatment of Lung Cancer: A Systematic Review

“…Cytotoxic T lymphocyte antigen 4 and programmed cell death 1 are two of the most potent T-cell immune control points (PD1). In different places and times during the life span of the T cell, they exert their biological effects [65].…”

“…The blockage of these proteins removes T-cell activation inhibitory signals and produces t-cell antitumor response mediation. However, with other tumor types, such as prostate cancer, the same method has not always worked [65]. The monoclonal antibody apilimumab binds to CTLA-4 and prevents it from interacting with its ligand [6].…”

Biomarkers and factors in small cell lung cancer patients treated with immune checkpoint inhibitors: A meta‐analysis

“…12 However, many patients with high PD-L1 expression do not achieve the expected antitumor response, while patients with low PD-L1 expression may still have clinical benefit. 13 TMB is defined as the total number of somatic mutations, base substitutions, deletions detected, or gene insertions per million bases. 14 TMB-High (TMB-H) increases the number and type of neoantigens produced by tumor cells, and the immune system has a greater chance of recognizing and killing tumor cells.…”