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      Anti–PD-1 and Anti–PD-L1 in Head and Neck Cancer: A Network Meta-Analysis

      systematic-review

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          Abstract

          Objective

          The monoclonal antibodies anti-programmed death protein-1 (anti–PD-1) nivolumab and pembrolizumab are the first immune checkpoint inhibitors (ICIs) approved for treatment of recurrent/metastatic head and neck carcinoma R/M HNSCC in first line and in platinum refractory disease. This network meta-analysis aims to investigate the efficacy of anti–PD-1- vs anti–PD-L1-based therapy in R/M HNSCC cancer patients through a systematic review of the literature to provide support for evidence-based treatment decisions. In particular, the effectiveness of ICIs for R/M HNSCC is analyzed according to the different mechanisms of action of the check-points inhibitory drugs in different subgroups of patients.

          Methods

          We did a systematic literature review and network meta-analysis (NMA) of randomized controlled trials (RCTs) in PubMed, ClinicalTrials.gov, Embase, Medline, the Cochrane Central Register of Controlled Trials, Web of Science. Our search identified a total of five randomized controlled trials: Keynote 040, Keynote 048, Eagle, Condor, Checkmate 141. These trials included 3001 patients. Treatment was sub-categorized into PD-L1–based, PD-1–based, and standard chemotherapy. Treatments were indirectly compared with anti–PD-L1-based therapy.

          Results

          The network meta-analysis demonstrated no significant differences in OS between different subgroups except for the metastatic patients in which anti–PD-1-based therapy was associated with significantly less risk of death. Furthermore, anti–PD-1-based therapy appeared to be effective in smoker patients and in human papilloma–negative (HPV) patients. Conversely, anti–PD-L1-based therapy seems to be better efficient in female patients, in locally recurrent setting and in HPV positive patients.

          Conclusion

          This is the first NMA study that aimed to indirectly compare anti–PD-1- and anti–PD-L1-based therapy in HNSCC patients. The results of our NMA could help define a profile of patient responder or resistant to specific classes of immune drugs and can be used to guide/design future studies in the novel scenario of precision immune-oncology.

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          Most cited references71

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          The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration

          Systematic reviews and meta-analyses are essential to summarise evidence relating to efficacy and safety of healthcare interventions accurately and reliably. The clarity and transparency of these reports, however, are not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (quality of reporting of meta-analysis) statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realising these issues, an international group that included experienced authors and methodologists developed PRISMA (preferred reporting items for systematic reviews and meta-analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this explanation and elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA statement, this document, and the associated website (www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
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            Meta-analysis in clinical trials

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              Understanding the tumor immune microenvironment (TIME) for effective therapy

              The clinical successes in immunotherapy have been both astounding and at the same time unsatisfactory. Countless patients with varied tumor types have seen pronounced clinical response with immunotherapeutic intervention; however, many more patients have experienced minimal or no clinical benefit when provided the same treatment. As technology has advanced, so has the understanding of the complexity and diversity of the immune context of the tumor microenvironment and its influence on response to therapy. It has been possible to identify different subclasses of immune environment that have an influence on tumor initiation and response and therapy; by parsing the unique classes and subclasses of tumor immune microenvironment (TIME) that exist within a patient’s tumor, the ability to predict and guide immunotherapeutic responsiveness will improve, and new therapeutic targets will be revealed.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                09 August 2021
                2021
                : 12
                : 705096
                Affiliations
                [1] 1Department of Clinical and Molecular Oncology, “Sapienza” University of Rome , Rome, Italy
                [2] 2Department of Radiological, Oncological, and Anatomo-Pathological Science “Sapienza”, University of Rome , Rome, Italy
                [3] 3Medical Physics Unit, “S. Orsola-Malpighi” Hospital , Bologna, Italy
                [4] 4Department of Experimental Medicine, University Sapienza , Rome, Italy
                [5] 5Department of Medico-Surgical Sciences and Biotechnology, Polo Pontino, Sapienza University , Roma, Italy
                [6] 6Odontostomatological and Maxillo-Facial Science, ‘Sapienza’ University of Rome , Rome, Italy
                [7] 7Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS , Candiolo (Turin), Italy
                Author notes

                Edited by: Nicola Silvestris, University of Bari Aldo Moro, Italy

                Reviewed by: Alessandro Rizzo, Sant’Orsola-Malpighi Polyclinic, Italy; Gunes Esendagli, Hacettepe University, Turkey

                *Correspondence: Alessio Cirillo, alessio.cirillo@ 123456uniroma1.it

                †These authors have contributed equally to this work

                This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2021.705096
                8380817
                34434192
                e738b7f0-c646-478a-817e-2157d00a6c48
                Copyright © 2021 Botticelli, Cirillo, Strigari, Valentini, Cerbelli, Scagnoli, Cerbelli, Zizzari, Rocca, D’Amati, Polimeni, Nuti, Merlano, Mezi and Marchetti

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 May 2021
                : 12 July 2021
                Page count
                Figures: 4, Tables: 1, Equations: 1, References: 71, Pages: 9, Words: 3017
                Categories
                Immunology
                Systematic Review

                Immunology
                metastatic head and neck cancer,immunotherapy,anti–pd-1,anti–pd-l1,network meta-analysis

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