Anti-Programmed Cell Death-1 Versus Anti-Programmed Death-Ligand 1 (PD-L1) in PD-L1-Negative Advanced Non-Small Cell...

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.