Reduced FEV₁ as Prognostic Factors in Patients With Advanced NSCLC Receiving Immune Checkpoint Inhibitors

Background: The aim of study is to investigate the influence of pulmonary function on the prognosis in patients with advanced non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICI). Patients and Methods: Data were collected retrospectively from 151 patients with stage IV NSCLC who received ICI and completed spirometry before ICI therapy in Taipei Veterans General Hospital between January 2016 and December 2020. The co-primary end points were overall survival (OS) and progression-free survival (PFS) between groups divided by 80% predicted FEV₁ since ICI therapy started; the secondary outcomes were objective response rate. Results: Among 151 patients enrolled to this study, 67.5% of patients were men, 75.5% were adenocarcinoma, 24.5% had known targetable driver mutation, 33.8% received first-line ICI, and 62.8% received ICI monotherapy. The objective response rate was 24.5% and disease control rate was 54.3%. In multivariable analysis, patient with reduced FEV₁ had inferior PFS (FEV₁ < 80% vs. FEV₁ ≥ 80%, adjusted HR = 1.80, P = 0.006) and OS (FEV₁ < 80% vs. FEV₁ ≥ 80%, adjusted HR = 2.50, P < 0.001). Median PFS and OS in the preserved FEV₁ group (≥80% predicted FEV₁) compared to the reduced FEV₁ group (<80% predicted FEV₁) were 5.4 vs. 2.9 months (HR = 1.76, P = 0.003) and 34.9 vs. 11.1 months (HR = 2.44, P < 0.001), respectively. The other independent prognostic factors of OS include stage IVA disease (adjusted HR = 0.57, P = 0.037), initial liver metastasis (adjusted HR = 2.00, P = 0.049), ICI monotherapy (adjusted HR = 1.73, P = 0.042) and ICI related pneumonitis (adjusted HR = 3.44, P = 0.025). Conclusions: Reduced FEV₁ is strongly associated with inferior clinical outcomes in patients with advanced NSCLC treated with ICI.