Impact of treatment line on risks and benefits of immune checkpoint inhibitor in patients with advanced non-small cell lung cancer and interstitial lung disease: a systematic review and meta-analysis of cohort studies

BACKGROUND: There is no clear consensus regarding the safety and efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC) and pre-existing interstitial lung disease (ILD). We aimed to elucidate the impact of ICIs on pre-existing ILD. METHODS: We systematically queried PubMed-MEDLINE, Embase-Scopus, and ISI Web of Science databases up to January 10, 2022. The pooled any-grade and grade 3–5 ICI-associated pneumonitis (ICIP) rate and objective response rate (ORR) in patients with pre-existing ILD were mainly evaluated. The relative risk (RR) was also evaluated for pre-existing ILD and usual interstitial pneumonia (UIP) patterns. Sensitivity and subgroup analyses were performed to assess the heterogeneity. RESULTS: In total, 17 studies involving 5,529 patients were included in the meta-analysis. The pooled ICIP rate was 30% [95% confidence interval (CI): 24–36%]; it was found to be significantly higher in patients with pre-existing ILD relative to those without (RR =3.05, 95% CI: 2.53–3.69; I2=0.0%). The pooled grade 3–5 ICIP rate was 12% (95% CI: 9–15%); this was also significantly higher in patients with pre-existing ILD (RR =3.19, 95% CI: 2.32–4.38; I(2)=0.0%). According to subgroup analysis, these ICIP rates were not significantly different among the treatment lines (first, ≥ second, and mixed) (P=0.33) whereas the pooled ORR was 36% (95% CI: 24–48%; I(2)=53.7%) with a significant difference among the treatment lines (P=0.027). The pooled ICIP rate was independent of the UIP pattern (RR =1.06, 95% CI: 0.86–1.32; I(2)=0.0%). CONCLUSIONS: Overall, ICIs should be administered cautiously in patients with pre-existing ILD, regardless of the treatment line. Moreover, the risks of ICIP may outweigh ICI benefits, especially in second-or later-line treatment. These results need to be further confirmed by meta-analyses including more observational cohort studies in clinical setting.