PD-(L)1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer Patients with High PD-L1 Expression: A Network Meta-Analysis

• Main Authors: Margarita Majem, Manuel Cobo, Dolores Isla, Diego Marquez-Medina, Delvys Rodriguez-Abreu, Joaquín Casal-Rubio, Teresa Moran Bueno, Reyes Bernabé-Caro, Diego Pérez Parente, Pedro Ruiz-Gracia, Marta Marina Arroyo, Luis Paz-Ares
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Journal of Clinical Medicine
• Subjects: non-small cell lung cancer; network meta-analysis; immunotherapy; first-line treatment; PD-(L)1 inhibitors; efficacy
• Online Access: https://www.mdpi.com/2077-0383/10/7/1365

Programmed cell death-ligand 1 (PD-L1) has emerged as a potential biomarker for selection of patients more likely to respond to immunotherapy and as a prognostic factor in non-small cell lung cancer (NSCLC). In this network meta-analysis, we aimed to evaluate the efficacy of first-line anti-PD-(L)1 monotherapy in advanced NSCLC patients with high PD-L1 expression (≥50%) compared to platinum-based chemotherapy. We also evaluated efficacy outcomes according to tumor mutational burden (TMB). To that end, we conducted a systematic review. Six clinical trials with 2111 patients were included. In head-to-head comparisons, immunotherapy showed a significant improvement in progression-free survival (PFS: HR_pooled = 0.69, 95% CI: 0.52–0.90, <i>p </i>=<i> </i>0.007), overall survival (OS: HR_pooled = 0.69, 95% CI: 0.61–0.78; <i>p </i><<i> </i>0.001) and overall response rate (ORR) (Risk ratio (RR)_pooled = 1.354, 95% CI: 1.04–1.762, <i>p </i>=<i> </i>0.024). In the assessment of relative efficacy for PFS through indirect comparisons, pembrolizumab (results from KEYNOTE-024) ranked highest followed by cemiplimab and atezolizumab, with statistical significance determined for some of the drugs. In terms of OS, cemiplimab ranked highest followed by atezolizumab and pembrolizumab, although non-significant OS was determined for these drugs. In conclusion, PD-(L)1 inhibitor monotherapy improves efficacy outcomes in the first line setting of advanced NSCLC patients with high PD-L1 expression. Evaluations with longer follow up are still needed to determine the superiority of any specific drug.