Efficacy and safety of nivolumab in non‐small cell lung cancer with preexisting interstitial lung disease

Abstract

BackgroundThe risk of developing lung cancer is high in patients with interstitial lung disease (ILD), as few treatment options are available. Immune checkpoint inhibitors (ICI) are used for the treatment of non‐small cell lung cancer (NSCLC) in clinical practice; however, in patients with preexisting ILD, the risk of ICI‐related pneumonitis is unknown. We evaluated the efficacy and lung toxicity of nivolumab in patients with NSCLC and ILD.MethodsWe retrospectively reviewed the medical records of 216 NSCLC patients who had received nivolumab therapy. The existence of ILD in these patients was determined by lung computed tomography findings; 26 patients had ILD. We evaluated the efficacy of nivolumab by measuring the response rate (RR), progression‐free survival (PFS) duration, and lung toxicity by incidence, severity, and outcome of nivolumab‐related ILD.ResultsThe RR and median PFS of the ILD and non‐ILD groups were 27% versus 13% (P = 0.078) and 2.7 (95% confidence interval [CI], 1.7–5.3) versus 2.9 months (95% CI 2.1–3.4; P = 0.919), respectively. The incidences of total and severe nivolumab‐related pneumonitis were significantly higher in the ILD group than in the non‐ILD group (31% vs. 12%, P = 0.014 and 19% vs. 5%, P = 0.022, respectively). No death from nivolumab‐related pneumonitis occurred. Over 50% of the patients in both groups with nivolumab‐related pneumonitis showed improvement over time.ConclusionRelative to the non‐ILD group, nivolumab‐related pneumonitis was observed more frequently in the ILD group; however, most cases were manageable.

PD‐1 inhibitors for non‐small cell lung cancer patients with special issues: Real‐world evidence

“…In our study, none of the patients with preexisting ILD experienced ILD‐AEs or pneumonitis, although the number of the patients was small (n = 6). PFS did not differ significantly between patients with and without ILD (not reached vs 2.56 months, P = .248), consistent with previous studies …”

“…Only a few retrospective studies reporting the clinical use of ICIs in NSCLC patients with ILD are available. One retrospective study indicated that ICI‐associated pneumonitis was more common in ILD NSCLC patients than in non‐ILD NSCLC patients (31% vs 12%) . In another study, pneumonitis was observed more frequently in patients with preexisting ILD than in those without, but the difference was not statistically significant (29% vs 11%, P = .08) .…”

“…Moreover, EGFR tyrosine kinase inhibitors, a novel standard therapy for EGFR‐mutant NSCLC patients, were found to cause pneumonitis more commonly in NSCLC patients with preexisting ILD than in those without . On a theoretical basis, ICIs have the potential to worsen ILD in NSCLC patients, so most clinical trials have excluded patients with preexisting ILD . In general, ICI‐associated pneumonitis occurs in 3‐12% of NSCLC patients .…”

“…Another study investigating anti‐PD‐1 therapy for seven melanoma or NSCLC patients with viral hepatitis revealed that one HCV patient experienced grade 2 ALT elevation and four patients experienced grade 1 ALT elevation . Regarding ILD, a case series indicated that anti‐PD‐1‐related pneumonitis occurred more frequently in NSCLC patients with ILD than in those without (31% vs 12%, P = .014) . In another case report, three lung cancer patients with ILD who were treated with nivolumab did not experience any aggravation of ILD or pneumonitis .…”

Immune checkpoint inhibitor‐associated interstitial lung diseases correlate with better prognosis in patients with advanced non‐small‐cell lung cancer

“…Kanai et al . also showed that the incidence and severity of ILD were significantly higher in those with pre‐existing IP . Therefore, further careful monitoring for ILD is needed during ICI treatment in patients with pre‐existing IP.Recently, Tanaka et al .…”