Related Experiment Video
Updated: Apr 11, 2026
Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
Published on: May 2, 2025
Comparative safety of PD-1 and PD-L1 inhibitors in advanced solid tumors: a real-world cohort study with competing
Yu-Hsiang Shih1,2, Shao-Jing Wang1, Chun-Ting Fan1
1Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung, 40705, Taiwan.
Background:
Real-world evidence comparing long-term safety between PD-1 and PD-L1 inhibitors is limited, and the impact of competing mortality is unclear.
Methods:
This retrospective cohort study utilized the TriNetX platform (2014-2024). Adults with advanced solid tumors initiating a PD-1 or PD-L1 inhibitor within 3 months of diagnosis were included. A 1:1 propensity score match created balanced cohorts. The primary outcome was the 1-year incidence of immune-related adverse events (irAEs). Standard Cox models and Fine-Gray competing risk models (accounting for death) were used to estimate hazard ratios (HRs) and subdistribution hazard ratios (sHRs), respectively.
Results:
After matching, 22,672 patients (11,336 per group) were analyzed. In standard Cox analysis, PD-L1 inhibitors were associated with a lower risk of skin rash (HR 0.66, 95% CI 0.56-0.78), colitis (HR 0.79, 0.71-0.87), and nephritis (HR 0.71, 0.54-0.94) compared to PD-1 inhibitors. The competing risk analysis revealed that all-cause mortality was the overwhelmingly dominant outcome. Consequently, PD-L1 inhibitor use was associated with uniformly lower sHRs for every irAE analyzed (range: 0.85-0.88), with the sHR for mortality itself at 0.88 (0.84-0.92). This pattern, indicating the safety signal was heavily confounded by survival, was consistent across sex and age subgroups but more pronounced in males and older patients.
Conclusion:
PD-L1 inhibitors are associated with a lower risk of specific irAEs. However, mortality is the dominant competing risk in advanced cancer, fundamentally shaping safety assessments. Real-world studies must account for competing mortality to avoid distorted conclusions.
Insights
Comparing PD-1 and PD-L1 inhibitors, PD-L1 inhibitors show lower risks for specific immune-related adverse events (irAEs). However, competing mortality in advanced cancer significantly impacts safety assessments, necessitating its consideration in real-world studies.
Area of Science:
- Oncology
- Immunotherapy
- Real-World Evidence
Background:
- Limited real-world data exists comparing long-term safety of PD-1 and PD-L1 inhibitors.
- The influence of competing mortality on safety outcomes is not well understood.
Purpose of the Study:
- To compare the long-term safety profiles of PD-1 and PD-L1 inhibitors in advanced solid tumors.
- To evaluate the impact of competing mortality on the assessment of immune-related adverse events (irAEs).
Main Methods:
- Retrospective cohort study using the TriNetX platform (2014-2024).
- Included adults with advanced solid tumors initiating PD-1 or PD-L1 inhibitors.
- Used propensity score matching and both standard Cox and Fine-Gray competing risk models.
Main Results:
- PD-L1 inhibitors were associated with lower risks of skin rash, colitis, and nephritis compared to PD-1 inhibitors in standard analysis.
- Competing risk analysis revealed mortality as the dominant outcome, confounding safety signals.
- PD-L1 inhibitors showed lower subdistribution hazard ratios for all analyzed irAEs, with a notable sHR for mortality itself.
Conclusions:
- PD-L1 inhibitors demonstrate a reduced risk of certain irAEs.
- Competing mortality is a critical factor in safety assessments for advanced cancer patients.
- Real-world safety studies must incorporate competing risk analyses to avoid biased conclusions.
