Impact of Frailty on Outcomes of First-Line Pembrolizumab Monotherapy in a Real-World Population with Advanced Non-Small Cell Lung Cancer

SIMPLE SUMMARY: Real-world studies of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) have shown worse outcomes in patients with poor Eastern Cooperative Oncology Group Stage Performance Status (ECOG PS). This index measures functional status but does not assess the cause. The ECOG PS scale is influenced by different aspects, such as the burden of the disease itself, the presence of comorbidities and the global frailty of patients. The influence of frailty on the efficacy of ICIs in patients with NSCLC has not been evaluated. In this study, we investigated the role of frailty on the clinical outcomes of first-line pembrolizumab in a retrospective cohort of 101 patients with advanced NSCLC. In our study, frailty determined based on indirect markers was identified as an independent predictor of overall survival (OS) and progression-free survival (PFS). Frailty assessment before starting antineoplastic therapy could be a useful tool for clinical decision making. ABSTRACT: ICIs have been able to improve overall survival in advanced-stage lung cancer. The benefit of this therapy is limited in patients with poor ECOG PS. However, this scale is imprecise and can be influenced by different factors, such as frailty. Cancer patients have a high risk of frailty independently of age. In this observational, single-center, retrospective study, we investigated the effect of frailty on the effectiveness of pembrolizumab in first-line use in a cohort of 101 patients with metastatic NSCLC. Frailty was determined using a frailty score system developed by Sakakida et al. Univariate and multivariate analysis was performed to determine the prognostic role of frailty on OS and PFS. Median OS was significantly higher in patients with low frailty compared with intermediate and high frailty (23.8 vs. 7.0 and 1.8 months, respectively; p < 0.001). Median PFS was also significantly higher in patients with low frailty compared with intermediate and high frailty (10.5 vs. 3.9 and 1.6 months; p < 0.001, respectively). Frailty was the only variable that showed significant differences in OS and PFS. Multivariate analysis confirms frailty as an independent predictor of OS and PFS. Frailty assessment could help to select which patients are candidates for ICIs in NSCLC.