Low pre-immunotherapy forced vital capacity is associated with poor outcomes in non-small cell lung cancer patients receiving immunotherapy regardless of prior treatment history

Background: Many patients with lung cancer have underlying chronic lung diseases. We assume that baseline lung functions might also affect the prognosis of non-small cell lung cancer (NSCLC) patients receiving immunotherapy.

Objectives: We aimed to assess the impact of pretreatment clinical parameters, including lung function measures such as forced vital capacity (FVC), on the prognosis of patients with NSCLC following immune checkpoint inhibitors (ICIs) therapy.

Design: Retrospective multicenter study.

Methods: Study subjects were consecutively selected from a multicenter cohort of patients with NSCLC who were undergoing immunotherapy. Patients were selected regardless of their initial cancer stage and prior treatment. The primary outcome was immunotherapy-related overall survival (iOS), defined as the duration from the initiation of immunotherapy to the time patients were censored. Spirometry values were acquired before bronchodilator application and were performed within the year before the first ICI treatment.

Results: We selected 289 patients for evaluation. The median iOS was 10.9 months (95% confidence interval (CI), 7.5-14.3). Programmed death-ligand 1 (PD-L1) expression, tested by SP263, was <1% in 20.9%, 1%-49% in 44.3%, and ⩾50% in 32.6% of the patients. ICI was used most often as second-line treatment (70.2%), followed by first line (13.1%), and third line (11.4%). In the Kaplan-Meier analysis, the median iOS of the low FVC group was significantly shorter than that in the preserved FVC group (6.10 (95% CI, 4.45-7.76) months vs 14.40 (95% CI, 10.61-18.34) months, p < 0.001)). A Cox regression analysis for iOS showed that age, poor performance status, PD-L1 expression measured by SP263, stage at diagnosis, and FVC (% predicted) were independent predictive factors. When we replaced FVC (%) in the multivariable analysis with forced expiratory volume in 1 s (%), diffusing lung capacity for carbon monoxide (DLco; %), or DLco (absolute), each of the pulmonary function factors showed a significant association with iOS.

Conclusion: Pre-immunotherapy FVC (%) predicted immunotherapy-related outcomes in NSCLC patients, regardless of initial stage at diagnosis and prior treatment modalities.