Different patterns of treatment‐related adverse events of programmed cell death‐1 and its ligand‐1 inhibitors in different cancer types: A meta‐analysis and systemic review of clinical trials

Abstract

Programmed cell death receptor-1 and its ligand-1 (PD-1/PD-L1) inhibitors have been applied to many cancers, but the difference of treatment-related adverse events (AEs) across cancer types remains unknown. We performed a meta-analysis and systemic review to compare the incidences of commonly reported all-grade AEs across cancer types and found that the most frequent AEs were fatigue, rash/pruritus, loss of appetite/nausea and diarrhea. However, each cancer type also had its higher incidences of AEs involving a relevant system, such as melanoma with epidermal AEs (rash, diarrhea and enterocolitis), lung cancer with dyspnea and pneumonitis, digestive system cancers with amylase and lipase elevation; and renal cell and urothelial cancer with kidney injury (creatinine elevation and proteinuria). However, the incidence of hepatitis did not follow the pattern to show a difference. We did another comparison between PD-1 and PD-L1 inhibitors in lung cancer and urothelial cancer respectively, and found that the risk of most AEs did not differ much, except for more hypothyroidism in PD-1 inhibitors, and more kidney injury in PD-L1 inhibitors. Besides possible immunological mechanisms for treatment-related AEs, the influence of previous radiotherapy and the clinical characteristics of the diseases themselves should also be considered and is worth further investigation. With the result of this meta-analysis, clinicians could estimate the risk of certain AE in certain cancer type, to make treatment options and to customize monitor strategies.

Neoadjuvant programmed cell death protein 1 inhibitors combined with chemotherapy in resectable non-small cell lung cancer: an open-label, multicenter, single-arm study

“…AEs and complications occurred in this study at a similar frequency to those reported in the published data on neoadjuvant chemotherapy (15). In this study, we found that immune-related AEs could be well monitored and managed (16), which is similar to the observations made in the NADIM study (17). Only in 1 case did neoadjuvant therapy need to be halted after 1 cycle of treatment, with this patient's complication being lung abscess caused by obstructive pneumonia, which was unrelated to PD-1 inhibitor treatment.…”

Programmed cell death protein-1 inhibitors in the treatment of digestive system tumors in Chinese population: an observational study of effectiveness and safety

“…However, the incidence of irAEs varies according to different ICIs. In addition, the incidence of irAEs is also higher in patients who received combined immunotherapy than monotherapy (26,27). In this study, the irAE incidence for the 21 patients who were treated with ICI monotherapy was 42.8%, with mainly mild to moderate clinical manifestation of thyroid dysfunction.…”

Safety and efficacy of radiotherapy/chemoradiotherapy combined with immune checkpoint inhibitors for non-small cell lung cancer: A systematic review and meta-analysis

“…Gu et al. ( 85 ) found an increased likelihood of hypothyroidism after PD-1 inhibition against lung cancer, and renal injury for PD-L1. Pneumonitis was more common following PD-1 treatment, but hepatitis, rash and lipase elevation were more common for PD-L1.…”