Comparative Safety of PD-1/PD-L1 Inhibitors for Cancer Patients: Systematic Review and Network Meta-Analysis

Area of Science:

• Oncology
• Immunotherapy
• Clinical Pharmacology

Background:

• Limited comprehensive data exists comparing treatment-related adverse events (trAEs) across different programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors.
• Understanding these safety differences is crucial for optimizing cancer treatment strategies.

Approach:

• A systematic review and Bayesian network meta-analysis (NMA) was conducted.
• Twenty-three randomized controlled trials (RCTs) involving 14,204 cancer patients were analyzed.
• Incidences and odds ratios of all-grade and high-grade trAEs and immune-related adverse events (irAEs) were estimated.

Key Points:

• Programmed cell death-ligand 1 (PD-L1) inhibitors exhibited the lowest incidence of trAEs (all-grade: 60.4%; high-grade: 6.4%).
• Combination therapies, particularly PD-1 inhibitors plus chemotherapy, showed the highest incidence of high-grade trAEs (8.2%).
• PD-1 inhibitors had the highest incidence of irAEs (all-grade: 15.1%; high-grade: 3.5%).

Conclusions:

• Programmed cell death-ligand 1 (PD-L1) inhibitors present the most favorable safety profile regarding both trAEs and irAEs.
• PD-1 inhibitors did not show significantly increased trAEs or irAEs compared to PD-L1 inhibitors.
• Comparative safety data can guide the appropriate clinical use of PD-1/PD-L1 inhibitors.