Risk of interstitial lung disease with the use of programmed cell death 1 (PD-1) inhibitor compared with programmed cell death ligand 1 (PD-L1) inhibitor in patients with breast cancer: A systematic review and meta-analysis

Lijuan Guo; Xiaoyi Lin; Xin Lin; Yulei Wang; Jiali Lin; Yi Zhang; Xiangqing Chen; Miao Chen; Guochun Zhang; Yifang Zhang

doi:10.1016/j.cpt.2023.08.002

Risk of interstitial lung disease with the use of programmed cell death 1 (PD-1) inhibitor compared with programmed cell death ligand 1 (PD-L1) inhibitor in patients with breast cancer: A systematic review and meta-analysis

Cancer Pathog Ther. 2023 Aug 18;2(2):91-102. doi: 10.1016/j.cpt.2023.08.002. eCollection 2024 Apr.

Authors

Lijuan Guo^{1

2}, Xiaoyi Lin^{1

3}, Xin Lin^{1

4}, Yulei Wang¹, Jiali Lin⁵, Yi Zhang⁵, Xiangqing Chen⁵, Miao Chen⁶, Guochun Zhang^{1

2}, Yifang Zhang⁵

Affiliations

¹ Department of Breast Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510000, China.
² School of Medicine, South China University of Technology, Guangzhou, Guangdong 510000, China.
³ Medical College, Shantou University, Shantou, Guangdong 515000, China.
⁴ The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510000, China.
⁵ Department of Breast Cancer, Guangdong Provincial People's Hospital's Nanhai Hospital, Foshan, Guangdong 528000, China.
⁶ Department of Emergency Medicine, Guangdong Provincial People's Hospital's Nanhai Hospital, Foshan, Guangdong 528000, China.

Abstract

Background: Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have become integral elements within the current landscape of breast cancer treatment modalities; however, they are associated with interstitial lung disease (ILD), which is rare but potentially fatal. Notably, only a few studies have compared the difference in ILD incidence between PD-1 and PD-L1 inhibitors. Therefore, this study aimed to assess the discrepancies regarding ILD risk between the two immune checkpoint inhibitors. We also reported three cases of ILD after PD-1 inhibitor treatment.

Methods: We comprehensively searched PubMed, EMBASE, and the Cochrane Library to identify clinical trials that investigated PD-1/PD-L1 inhibitor treatment for patients with breast cancer. Pooled overall estimates of incidence and risk ratio (RR) were calculated with a 95% confidence interval (CI), and a mirror group analysis was performed using eligible studies.

Results: This meta-analysis included 29 studies with 4639 patients who received PD-1/PD-L1 inhibitor treatment. A higher ILD incidence was observed among 2508 patients treated with PD-1 inhibitors than among 2131 patients treated with PD-L1 inhibitors (0.05 vs. 0.02). The mirror group analysis further revealed a higher ILD event risk in patients treated with PD-1 inhibitors than in those treated with PD-L1 inhibitors (RR = 2.34, 95% CI, 1.13-4.82, P = 0.02).

Conclusion: Our findings suggest a greater risk of ILD with PD-1 inhibitors than with PD-L1 inhibitors. These findings are instrumental for clinicians in treatment deliberations, and the adoption of more structured diagnostic approaches and management protocols is necessary to mitigate the risk of ILD.

Keywords: Breast cancer; Immune-related adverse events; Interstitial lung disease; Programmed cell death 1 inhibitor; Programmed cell death ligand 1 inhibitor.

Publication types

Review