Interstitial lung disease in patients with recurrent and metastatic head and neck cancer treated with immune checkpoint inhibitors and cetuximab and/or paclitaxel

Background In recurrent and metastatic head and neck cancer (R/M HNC), all of cetuximab (Cmab), paclitaxel (PTX), and immune checkpoint inhibitors (ICI) can cause interstitial lung disease (ILD). This study aimed to clarify the clinical outcome of ILD and risk factors for ILD. Methods We retrospectively analyzed 400 patients with R/M HNC who initiated chemotherapy at our institution with any of ICI, Cmab, and PTX. The incidence of ILD induced by each drug, risk factors for ILD, and survival after ILD were evaluated. ILD was diagnosed by diagnostic radiologists. Results The median follow-up period was 17.7 months. The incidence of ILD was 11.0% (20/182) in patients treated with both ICI and Cmab/PTX. Similarly, those of ILD were 8.8% (8/91) in the patients with ICI alone without Cmab/PTX, and 2.4% (3/127) in those of non-ICI. Multivariable analysis identified a history of heavy smoking (Brinkman index ≥ 600) (odds ratio [OR] 3.49, 95% confidence interval [CI] 1.21–10.1) and history of stroke (OR 4.08, 95% CI 1.01–16.5) as the independent risk factors for ILD. 16 patients of ILD needed to change their regimen or withdraw chemotherapy. Nevertheless, the 5-year overall survival was higher in the ILD group than in the non-ILD group (25.1% vs. 5.7%, p = 0.0106). Conclusions The incidence of ILD was higher in patients with R/M HNC who received ICI than in those who didn’t. The history of heavy smoking and stroke were independent risk factors for ILD regardless of sequence of ICI, Cmab and PTX.