A strong association between TTF-1 expression and interstitial lung disease in predicting the efficacy of PD-1 inhibitor for nonsquamous NSCLC patients.

Background: Thyroid transcriptional factor-1 (TTF-1) is associated with the development of interstitial lung disease (ILD) and is a mutational target in lung adenocarcinoma with ILD. TTF-1 expression is also associated with the efficacy of pemetrexed-based chemotherapy for nonsquamous nonsmall cell lung cancer (NS-NSCLC). However, the relationship between TTF-1 expression and the efficacy of immunotherapy using programmed cell death 1 inhibitor (PD-1i), especially in lung cancer patients with ILD, remains unclear.

Methods: Medical data of NS-NSCLC patients treated with PD-1i at multiple centres were analysed retrospectively. Patients were divided into those with or without concomitant ILD, with the two cohorts further stratified by TTF-1 expression.

Results: The study population included 62 NS-NSCLC patients, 34 with and 28 without ILD. Median progression-free survival (PFS) during PD-1i treatment was significantly shorter in TTF-1-negative than -positive patients (2.0 12.1 months, p=0.004) in the ILD cohort but did not differ significantly in the non-ILD cohort (1.8 2.6 months, p=0.63). Median overall survival (OS) was also significantly shorter in TTF-1-negative than -positive patients in the ILD cohort (14.5 42.5 months, p=0.018) but not in the non-ILD cohort (33.7 37.1 months, p=0.53). Cox regression analyses showed that absence of TTF-1 expression was an independent risk factor for PFS (hazard ratio (HR) 2.75, p=0.024) and OS (HR 2.81, p=0.012) in the ILD cohort.

Conclusion: TTF-1 expression in NS-NSCLC patients with ILD may predict prognosis when treated with PD-1i.