Systemic Therapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma- A Systematic Review and Meta-Analysis

Background: The most effective regimen is unclear for patients with recurrent or metastatic head and neck squamous cell carcinomas (R/M HNSCC). We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating only systemic therapy for R/M HNSCC. Methods: This systematic review followed PRISMA and the Cochrane Collaboration Handbook for Systematic Reviews of Interventions. Endpoints included overall survival (OS), progression-free survival (PFS) and overall response rates (ORR). Results: 55 RCTs from 1990-November 2019 qualified for review (n=12132). Only PD-1/PDL-1 inhibitors increased OS in R/M HNSCC platinum-resistant disease against their control (HR = 0.79, 95%CI 0.70-0.90, p<0.001), especially for PD-L1 >= 1% expressing tumours (HR = 0.72, 95%CI 0.60-0.86, p<0.001). PFS was prolonged for anti-EGFR agents against methotrexate when used in a second line setting (HR = 0.74, 95 %CI 0.62-0.87, p=0.001), and when cetuximab (HR = 0.60, 95%CI 0.49-0.72, p<0.0001) and panitumumab (HR = 0.76, 95%CI 0.65-0.89, p=0.001) were introduced to platinum-based regimens for first-line treatment. Conclusions: PD-1/PD-L1 inhibitors may represent the future of R/M HNSCC treatment. However, EGFR inhibitors may still play improve clinical outcomes.