7dc16f6f93c8d40ef5dcf2d7ecf81e9f 269853.pdf fbf0481536970211c78bfc6ed0dc25ccd3577da8 269853.pdf 48aefc7b8f0dbbb7f1b3a421a698ecd71138273848c5ec4bafc1571db1c31716 269853.pdf Title: 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 Subject: 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: HRpooled = 0.69, 95% CI: 0.52–0.90, p = 0.007), overall survival (OS: HRpooled = 0.69, 95% CI: 0.61–0.78; p < 0.001) and overall response rate (ORR) (Risk ratio (RR)pooled = 1.354, 95% CI: 1.04–1.762, p = 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. Keywords: non-small cell lung cancer; network meta-analysis; immunotherapy; first-line treatment; PD-(L)1 inhibitors; efficacy Author: 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 and Luis Paz-Ares Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Apr 8 13:45:36 2021 CEST ModDate: Fri Apr 9 04:58:11 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 776704 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- YWQWLZ+VnURWPalladioL Type 1 Custom yes yes no 10 0 ZSRRVO+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 ELBIGF+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 PGXBXZ+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 FESTFF+CMSY10 Type 1 Builtin yes yes no 28 0 YSPQJI+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 40 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 43 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 65 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 69 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 73 0 BACGPI+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 100 0 BACHAK+PalatinoLinotype TrueType WinAnsi yes yes no 103 0 BACHBM+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 106 0 BACGPI+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 128 0 BACHAK+PalatinoLinotype TrueType WinAnsi yes yes no 131 0 BACHBM+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 134 0 BACGPI+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 153 0 BACHAJ+PalatinoLinotype CID TrueType Identity-H yes yes yes 156 0 BACHAK+PalatinoLinotype TrueType WinAnsi yes yes no 162 0 BACHBM+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 165 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 03:13:40 CEST RepresentationInformation: 269853.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 12:04:46 CEST Size: 776704 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 492 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Search Strategies and Study Selection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Selection Criteria Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Children: Item: Title: Studies Included in the Meta-Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Study Characteristics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Efficacy Endpoints in the Overall Population Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Subgroup Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Efficacy Results According to Tumor Mutational Burden Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Info: Title: 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 Author: 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 and Luis Paz-Ares Subject: 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: HRpooled = 0.69, 95% CI: 0.52 0.90, p = 0.007), overall survival (OS: HRpooled = 0.69, 95% CI: 0.61 0.78; p < 0.001) and overall response rate (ORR) (Risk ratio (RR)pooled = 1.354, 95% CI: 1.04 1.762, p = 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. 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