AUTHOR=Botticelli Andrea , Cirillo Alessio , Strigari Lidia , Valentini Filippo , Cerbelli Bruna , Scagnoli Simone , Cerbelli Edoardo , Zizzari Ilaria Grazia , Rocca Carlo Della , D’Amati Giulia , Polimeni Antonella , Nuti Marianna , Merlano Marco Carlo , Mezi Silvia , Marchetti Paolo 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.705096

DOI=10.3389/fimmu.2021.705096

ISSN=1664-3224

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 in order to provide support for evidence-based treatment decisions.  In particular the effectiveness of ICIs for R/M HNSCC is analysed according to the different mechanisms of action of the check-points inhibitory drugs in different subgroups of patients.  

Materials and 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 5 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 aimed to indirectly comparing anti PD-1 and anti PD-L1 based therapy in HNSCC patients. The results of our NMA could help to 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.