PD-(L)1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer Patients with High PD-L1...

Area of Science:

• Oncology
• Immunotherapy
• Biomarker Research

Background:

• Programmed cell death-ligand 1 (PD-L1) is a potential biomarker for immunotherapy response and a prognostic factor in non-small cell lung cancer (NSCLC).
• First-line treatment options for advanced NSCLC with high PD-L1 expression are critical for improving patient outcomes.

Purpose of the Study:

• To evaluate the efficacy of first-line anti-PD-(L)1 monotherapy versus platinum-based chemotherapy in advanced NSCLC patients with high PD-L1 expression (≥50%).
• To assess efficacy outcomes based on tumor mutational burden (TMB).

Main Methods:

• Conducted a systematic review and network meta-analysis of six clinical trials involving 2111 patients.
• Compared head-to-head efficacy of immunotherapy versus chemotherapy.
• Performed indirect comparisons to rank specific anti-PD-(L)1 agents for progression-free survival (PFS) and overall survival (OS).

Main Results:

• First-line anti-PD-(L)1 monotherapy demonstrated significant improvements in PFS (HRpooled = 0.69), OS (HRpooled = 0.69), and overall response rate (ORR) (RRpooled = 1.354) compared to chemotherapy.
• Pembrolizumab ranked highest for PFS in indirect comparisons, followed by cemiplimab and atezolizumab.
• Cemiplimab ranked highest for OS, followed by atezolizumab and pembrolizumab, though OS differences were not statistically significant.

Conclusions:

• First-line anti-PD-(L)1 inhibitor monotherapy significantly improves efficacy outcomes in advanced NSCLC patients with high PD-L1 expression.
• Further evaluations with longer follow-up are needed to determine the superiority of specific anti-PD-(L)1 drugs.