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

• Published in: Journal of clinical medicine Vol. 10; no. 7; p. 1365
• Main Authors: Majem, Margarita, Cobo, Manuel, Isla, Dolores, Marquez-Medina, Diego, Rodriguez-Abreu, Delvys, Casal-Rubio, Joaquín, Bueno, Teresa Moran, Bernabé-Caro, Reyes, Parente, Diego Pérez, Ruiz-Gracia, Pedro, Arroyo, Marta Marina, Paz-Ares, Luis
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.03.2021; MDPI
• Subjects: Apoptosis; Biomarkers; Cancer therapies; Chemotherapy; Clinical medicine; Clinical trials; Immunotherapy; Lung cancer; Medical prognosis; Meta-analysis; Metastasis; Mutation; Oncology; Review; non-small cell lung cancer; PD-(L)1 inhibitors; first-line treatment; network meta-analysis; efficacy; immunotherapy
• ISSN: 2077-0383; 2077-0383
• DOI: 10.3390/jcm10071365

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 = 0.69, 95% CI: 0.52-0.90, = 0.007), overall survival (OS: HR = 0.69, 95% CI: 0.61-0.78; < 0.001) and overall response rate (ORR) (Risk ratio (RR) = 1.354, 95% CI: 1.04-1.762, = 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.