The effects and safety of PD-1/PD-L1 inhibitors on head and neck cancer: A systematic review and meta-analysis

Background: Inhibitors 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.

Method: The 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.

Results: Overall, 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, I² = 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, I² = 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.

Conclusion: Programmed 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.