Abstract
BackgroundInhibitors of programmed cell death‐1 (PD‐1) and its ligand (PD‐L1) have been increasingly used in head and neck cancer therapy and reported to improve the outcomes with an acceptable safety profile. This systematic review and meta‐analysis was conducted to assess the benefit and risk of PD‐1/PD‐L1 inhibitors in patients with head and neck cancer.MethodThe PubMed, Cochrane Library, EMBASE and Web of Science databases were systematically searched to find potentially eligible studies up to May 30, 2019. Primary outcomes were overall survival (OS), progression‐free survival (PFS), objective response rate (ORR), disease control rate (DCR) and adverse events.ResultsOverall, this analysis consisted of nine eligible studies, with two randomized controlled trials and seven single arm trials. In the treatment of recurrent or metastatic head and neck cancer, PD‐1 inhibitors showed significantly lower relative risk of death than standard‐of‐care therapy (odds ratio [OR] = 0.60, 95% confidence interval [CI]: 0.44‐0.82, I 2 = 0%, P = .001). Programmed cell death‐1 inhibitors also decreased the risk of disease progression, however, there was no statistically significant difference of PFS between the treatments (OR = 0.69, 95% CI: 0.48‐1.01, I 2 = 0%, P = .05). Subgroup analysis showed that human papillomavirus (HPV) positive patients had higher response rates than HPV negative patients in PD‐1/PD‐L1 inhibitors‐treated population (ORR: 18.8% vs 12.2%; DCR: 42.8% vs 34.4%). The most common any‐grade and grade ≥3 treatment‐related adverse events were fatigue (14.7%, 95% CI: 12.3%‐17.1%) and aspartate aminotransferase increased (1.6%, 95% CI: 0.3%‐2.9%), respectively.ConclusionProgrammed cell death‐1 inhibitors prolonged OS in comparison with standard‐of‐care therapy in recurrent or metastatic head and neck cancer patients. Human papillomavirus positive patients were superior to HPV negative patients in the treatment of PD‐1/PD‐L1 inhibitors. More phase III randomized controlled trials are warranted to confirm our findings.
Highlights
Patients with recurrent or metastatic squamous cell carcinoma of the head and neck have a poor prognosis and few treatment options.[1-3]
In recently KEYNOTE‐048 clinical trial, combining an anti‐programmed cell death‐1 (PD‐1) agent + platinum + 5‐fluorouricil was recommended as a frontline treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma compared to the EXTREME regimen.[5-7]
High mutational burden owing to tobacco use, alcohol consumption, or human papillomavirus (HPV) expression might contribute to immunogenicity in head and neck cancer.[8-11]
Summary
Patients with recurrent or metastatic squamous cell carcinoma of the head and neck have a poor prognosis (a median survival of 6 months or less) and few treatment options.[1-3]. It is unknown whether the PD‐1/PD‐L1 inhibitors prolong the overall survival (OS) or progression‐free survival (PFS) and whether the HPV status is a predictive factor of efficacy for PD‐1/PD‐L1 targeted therapy in head and neck cancer. Overall, we conducted this systematic literature review and meta‐analysis to integrate the results of current knowledge and to evaluate the toxicity of PD‐1/PD‐L1 inhibitors in head and neck cancer
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