Drug-induced interstitial lung disease after chemoimmunotherapy for extensive-stage small cell lung cancer

Kiyoko Fukuda; Naoko Katsurada; Yoshitaka Kawa; Miyako Satouchi; Kazumi Kaneshiro; Masataka Matsumoto; Rei Takamiya; Yukihisa Hatakeyama; Ryota Dokuni; Kanoko Matsumura; Masahiro Katsurada; Kyosuke Nakata; Sho Yoshimura; Motoko Tachihara

doi:10.1016/j.heliyon.2023.e20463

Drug-induced interstitial lung disease after chemoimmunotherapy for extensive-stage small cell lung cancer

Heliyon. 2023 Sep 26;9(10):e20463. doi: 10.1016/j.heliyon.2023.e20463. eCollection 2023 Oct.

Affiliations

¹ Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan.
² Department of Thoracic Oncology, Hyogo Cancer Center, Japan.
³ Department of Respiratory Medicine, Kita-harima Medical Center, Japan.
⁴ Department of Respiratory Medicine, Akashi Medical Center, Japan.
⁵ Department of Respiratory Medicine, Hyogo Prefectural Awaji Medical Center, Japan.
⁶ Department of Respiratory Medicine, Takatsuki General Hospital, Japan.
⁷ Department of Internal Medicine, Hyogo Prefectural Tamba Medical Center, Japan.
⁸ Department of Respiratory Medicine, Konan Medical Center, Japan.
⁹ Department of Respiratory Medicine, Steel Memorial Hirohata Hospital, Japan.

Abstract

Objectives: The combination of chemotherapy and immune checkpoint inhibitors (chemo-ICI) has become the new standard of treatment for extensive-stage small cell lung cancer (ES-SCLC). Recently, slight changes in interstitial shadows, defined as interstitial lung abnormalities (ILA), have been identified. In patients with ES-SCLC who received chemo-ICI, there are limited data on the incidence of drug-induced interstitial lung disease (D-ILD) in daily practice and the association between the development of D-ILD and ILA in the baseline computed tomography (CT).

Materials and methods: A multicenter, retrospective study was conducted to investigate the incidence of D-ILD, the risk factors for developing D-ILD, progression-free survival (PFS), and overall survival (OS) in patients with ES-SCLC who received chemo-ICI between August 2019 and November 2021.

Results: This study enrolled 70 patients (median age, 71 years; including 58 men) from nine institutions in Japan. There were 62 patients (89%) treated with carboplatin/etoposide/atezolizumab and 8 patients treated with carboplatin or cisplatin/etoposide/durvalumab. Twenty-nine patients (41.4%) were found to have ILA at baseline CT. Eleven patients (15.7%) developed D-ILD. The proportion of patients with ILA was significantly higher in the group who developed D-ILD than in the group who did not (9/11 (81.8%) vs. 20/59 (33.9%), respectively, P = 0.0057). In addition, the frequency of ground glass attenuation (GGA) and reticulation was higher in patients who developed D-ILD. There was no significant difference in PFS and OS between patients who developed D-ILD and those who did not (median PFS, 8.0 (95% confidence interval (CI), 5.5-9.5) months vs. 5.0 (95% CI, 4.5-5.6) months, respectively, P = 0.11 and median OS, not reached (NR) (95% CI, 8.7-NR) vs. 18.2 (95% CI, 13.2-NR) months, respectively, P = 0.20).

Conclusion: The incidence of D-ILD in patients with ES-SCLC who received chemo-ICI in clinical practice was higher than that in clinical trials. Patients with pre-existing ILA were more likely to develop D-ILD.

Keywords: Drug-induced interstitial lung disease; Immunotherapy; Interstitial lung abnormalities; Small cell lung cancer.