Clinical Outcomes of Immune Checkpoint Inhibitor Therapy in Patients With Advanced Non-small Cell Lung Cancer and Preexisting Interstitial Lung Diseases: A Systematic Review and Meta-analysis

Background: Patients with non-small cell lung cancer (NSCLC) and preexisting interstitial lung disease (ILD) are often excluded from clinical trials of immune checkpoint inhibitors (ICIs), leaving a gap in knowledge.

Research question: What are the clinical outcomes of ICIs in patients with NSCLC and preexisting ILD?

Study design and methods: Systematic searches were conducted of PubMed, EMBASE, and Cochrane Library through April 2021 with no language or study design restrictions. Studies reporting the safety and efficacy data among patients with cancer and ILD receiving ICI therapy were collected. The primary end points were clinical efficacy to immunotherapy and the incidence of immune-related adverse events, especially for checkpoint inhibitor pneumonitis (CIP).

Results: A total of 179 patients in 10 studies were included. The pooled overall response rate (ORR) and pooled disease control rate (DCR) were 34% (95% CI, 20-47) and 66% (95% CI, 56-75), respectively. The ORR in patients with preexisting ILD was significantly higher than that in patients without ILD (OR, 1.99; 95% CI, 1.31-3.00). The DCR and progression-free survival in patients with preexisting ILD were not inferior to those without ILD (pooled OR, 1.46; 95% CI, 0.94-2.25 for DCR). The pooled incidences of any grade and grade 3 or higher CIP were 27% (95% CI, 17-37) and 15% (95% CI, 9-22) in patients with preexisting ILD, and 10% (95% CI, 6-13) and 4% (95% CI, 2-6) in patients without ILD. Meta-analysis found a significantly higher incidence rate of any grade and grade 3 or higher CIP in patients with NSCLC and preexisting ILD than in those patients without ILD (OR, 3.23 [95% CI, 2.06-5.06]; OR, 2.91 [95% CI, 1.47-5.74]).

Interpretation: Programmed cell death protein 1/programmed cell death ligand 1 inhibitors had favorable efficacy in NSCLC with preexisting ILD. CIP is frequent in patients with preexisting ILD who receive ICI therapy but is often mild and easily manageable. Clinicians should be cautious when using ICIs in patients with preexisting ILD.