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

Abstract

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; I2=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%; I2=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; I2=0.0%).Discussion: 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 laterline treatment. These results need to be further confirmed by meta-analyses including more observational cohort studies in clinical setting.

Current pharmacotherapies for advanced lung cancer with pre-existing interstitial lung disease : A literature review and future perspectives

“…The incidence of CIP in NSCLC patients with ILD has been analyzed in predominately retrospective studies and reported to be 11.1-42.9%, which is higher than in those without ILD (5.8-11.6%) (108-116) (Table 7). Recent meta-analyses of ICI therapy also found a significantly higher incidence of any grade and grade ≥ 3 pneumonitis in NSCLC patients with ILD, especially IPF, than in those without ILD (107,117). Accumulating evidence suggests risk factors other than pre-existing IPF for CIP include patients aged > 70 years old (118) ; those with Eastern Cooperative Oncology Group performance status score 2 or higher (119) ; comorbid lung diseases, such as asthma and chronic obstructive pulmonary disease (120) ; pre-existing interstitial lung abnormalities on baseline chest computed tomography (112) ; decreased FVC (121) ; prior thoracic radiotherapy (120) ; squamous cell lung carcinoma (122) ; and combination ICI therapy (123).…”

Clinical spectrum of Chinese hospitalized lung cancer patients with concomitant interstitial lung disease: before and after the new era of LC treatment

“…Taxane-containing chemotherapy, targeted therapies such as epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), and immune checkpoint inhibitors (ICIs) are common causes of drug-induced ILDs during systemic LC therapies [ 14 – 16 ]. Although targeted therapies and immunotherapy have significantly improved the prognosis of advanced LCs, patients with pre-existing ILD should be treated cautiously because of the increased risk of treatment-induced ILD [ 17 , 18 ]. Baseline ILD was considered a relative contraindication to ICI therapy [ 3 ].…”