Related Experiment Video
Updated: Sep 18, 2025
Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients
Published on: September 25, 2018
Anti-Programmed Cell Death-1 Versus Anti-Programmed Death-Ligand 1 (PD-L1) in PD-L1-Negative Advanced Non-Small Cell
Laith Al-Showbaki1, Malak Al-Kasasbeh2, Karem Jbarah1
1Division of Medical Oncology and Hematology, Jordan University Hospital and the School of Medicine, The University of Jordan, Amman, Jordan.
Background:
Immune checkpoint inhibitors (ICIs) which target programmed cell death-1 (PD-1) receptor or its ligand (PD-L1) are used extensively in non-small cell lung cancer (NSCLC). In this article, we compared the relative efficacy of PD-1 inhibitors and PD-L1 inhibitors in PD-L1-negative advanced NSCLC.
Methods:
We searched MEDLINE (host: PubMed, Scopus, and Google Scholar) for randomized trials for advanced NSCLC in which ICIs (anti-PD-1 or anti-PD-L1) were used where outcome data were reported based on PD-L1 testing, including the subset of PD-L1-negative patients. We extracted hazard ratios (HRs) and related 95% confidence intervals (CIs) and/or P values for progression-free survival (PFS) and overall survival (OS) for the PD-L1-negative subgroup of each included trial. We then pooled data using a random effects meta-analysis and compared anti-PD-1 to anti-PD-L1 inhibitors. Variations in effect size were examined using subgroup analyses.
Results:
Twenty-three trials were included in the meta-analysis. PD-L1 testing was performed in all participants. A total of 4,548 PD-L1-negative patients were included in the analysis, representing 33% of all participants in the included clinical trials. Overall, the addition of anti-PD-1 was associated with better OS in PD-L1-negative advanced NSCLC patients (HR: 0.75, 95% CI: 0.67 - 0.83, P < 0.01), while the addition of anti-PD-L1 inhibitors showed no improvement in OS (HR: 0.90, 95% CI: 0.78 - 1.05, P = 0.18). Compared to anti-PD-L1 agents, anti-PD-1 resulted in better OS in PD-L1-negative patients (HR: 0.83, 95% CI: 0.67 - 0.99, P = 0.01). The differential benefit of anti-PD-1 over anti-PD-L1 was of larger magnitude when checkpoint inhibitors were used in the first-line setting (pairwise comparison HR: 0.79, 95% CI: 0.66 - 0.93, P = 0.01), while there was no difference for later lines of therapy (pairwise comparison 1.13; 95% CI: 0.82 - 1.55, P = 0.45). These differences in OS were not observed when pooling PFS data.
Conclusions:
Compared to checkpoint inhibitors targeting PD-L1, those targeting PD-1 are associated with better OS in PD-L1-negative advanced NSCLC, a finding influenced by trials performed in the first-line sitting. These data should be validated using real-world studies.
Insights
For patients with PD-L1-negative advanced non-small cell lung cancer (NSCLC), programmed cell death-1 (PD-1) inhibitors show improved overall survival compared to programmed cell death ligand-1 (PD-L1) inhibitors, particularly in first-line treatment.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Trials
Background:
- Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) are standard treatments for non-small cell lung cancer (NSCLC).
- The efficacy of PD-1 versus PD-L1 inhibitors in PD-L1-negative advanced NSCLC remains an area of investigation.
Purpose of the Study:
- To compare the relative efficacy of PD-1 inhibitors versus PD-L1 inhibitors in patients with PD-L1-negative advanced NSCLC.
- To analyze overall survival (OS) and progression-free survival (PFS) outcomes based on PD-L1 expression status.
Main Methods:
- A systematic literature search was conducted across MEDLINE, PubMed, Scopus, and Google Scholar for randomized trials involving ICIs in advanced NSCLC.
- Data from 23 trials, including 4,548 PD-L1-negative patients, were pooled using random-effects meta-analysis.
- Hazard ratios (HRs) and confidence intervals (CIs) for OS and PFS were extracted and analyzed, with subgroup analyses performed.
Main Results:
- Anti-PD-1 therapy was associated with significantly better OS in PD-L1-negative advanced NSCLC (HR: 0.75, P < 0.01).
- Anti-PD-L1 therapy showed no significant improvement in OS for this subgroup (HR: 0.90, P = 0.18).
- Direct comparison revealed superior OS for anti-PD-1 over anti-PD-L1 inhibitors (HR: 0.83, P = 0.01), especially in first-line settings.
Conclusions:
- PD-1 inhibitors demonstrate superior overall survival compared to PD-L1 inhibitors in PD-L1-negative advanced NSCLC.
- The benefit of PD-1 inhibitors is more pronounced in first-line treatment settings.
- Further validation through real-world studies is recommended.
