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

Abstract

ObjectiveThe 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.MethodsWe 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.ResultsThe 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.ConclusionThis 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.

Approaches to the Management of Metastatic Adenoid Cystic Carcinoma

“…The most commonly used immune checkpoint inhibitors (ICIs) in HNC target signaling between the programmed death-1 receptor (PD-1) and programmed death ligands (PD-Ls). Pembrolizumab and nivolumab, monoclonal antibodies which inhibit PD-1, enhance tumor recognition by CD8+ TILs and stimulate cancer cell destruction [ 36 ]. The combined positive score (CPS) is a standard method for identifying HNC patients who are most likely to benefit from anti-PD-1 ICIs, and is determined through immunohistochemical analysis of the proportion of PD-L1-positive cells (including cancer cells, lymphocytes, and macrophages) in relation to total tumor cells in a patient’s sample [ 37 ].…”

Advances in the study of CD47‐based bispecific antibody in cancer immunotherapy

“…The anti-PD1 and PD-L1 antibodies competitively bind to and release the inhibitory state of T-cells and exert an anti-tumour immune function. Multiple PD1 and PD-L1 mAbs significantly improve patient prognosis and survival because the US FDA approved the first PD1 mAb Keytruda for the treatment of malignant melanoma in 2014 [38,39]. The co-expression of CD47 and PD1/PD-L1 is an independent prognostic factor affecting the survival of a variety of tumour patients, and is an important target marker for combined immunotherapy [40].…”

Immunotherapy and Modern Radiotherapy Technique for Older Patients with Locally Advanced Head and Neck Cancer: A Proposed Paradigm by the International Geriatric Radiotherapy Group

“…In a meta-analysis of head and neck cancer patients receiving chemotherapy, women benefited from the treatment more than men [ 115 ]. Another meta-analysis also corroborates a favorable response of women to anti-PD-L1-based therapy and raises concerns about the potential role of gender in influencing survival outcome [ 116 ]. However, using a match-paired analysis to compare survival rates between men and women following head and neck cancer treatment, there was no gender benefit [ 117 ].…”