Combined emphysema and cancer, from radiology to prognosis in patients treated by immunotherapy: An ancillary study of a prospective multicenter phase II IFCT-1802 SAVIMMUNE.

INTRODUCTION: In studies evaluating the efficacy of anti-programmed cell death (ligand)1 (anti-PD-(L)1) in patients with non-small-cell lung cancer (NSCLC), smokers tend to have better clinical outcomes than non-smokers. However, whether co-existing emphysema is associated with differences in clinical outcomes, regardless of smoking status remains unclear. METHODS: In a single-arm, prospective, multicenter, phase II trial, patients aged 18-75 years with metastatic NSCLC, PD-L1≥25% and a performance status (PS) of 2-3 received durvalumab until progression or toxicity. Pre-planned analyses classified emphysema visually as follows: <10% (no/mild emphysema), 10 to 25% (moderate emphysema) and >25% (severe emphysema). We also quantified emphysema (%LAV-950HU), along with bronchial (wall thickness) and small pulmonary vessels (cross-sectional area<5 mm²). RESULTS: Fifty patients were enrolled with 49 analyzable CT scans, of whom 43 (87.8%) had emphysema. Twenty-eight patients (57%) had an emphysema extent >10%, with a median %LAV-950 HU of 0.97 [IQR: 0.25-3.12]. In univariate analyses, compared to mild emphysema, patients with moderate emphysema had a significantly poorer overall survival (OS (HR 2.73, 95%CI [1.25-5.98]), whereas severe emphysema had not. Objective response rate and progression free survival were similar in all groups. In multivariate analyses, OS remained lower in patients with moderate emphysema (HR: 2.53, 95%CI [1.12-5.71]), after adjustment for smoking, age and PS. There was no difference according to bronchial and vascular involvement. CONCLUSION: In a single-arm cohort of PS2-3 patients with advanced NSCLC treated with 1st-line durvalumab, the presence of moderate emphysema was associated with worse overall survival.