Efficacy and safety of systemic treatments for patients with recurrent/metastatic head and neck squamous cell carcinoma: A systematic review and network meta-analysis.

Abstract

e18001 Background: A variety of systemic chemotherapy regimens have been used for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, most guidelines were derived from a single clinical trial, and no studies have comprehensively compared their efficacy and safety. This study is aimed to compare the efficacy and safety of systemic chemotherapies for patients with R/M HNSCC. Methods: We conducted a systematic review of published studies in PubMed, Embase, Web of Science, and Cochrane Library databases up to July 31, 2020. Studies were included if they were randomized controlled clinical trials including treatment regimens recommended by the latest NCCN guidelines. Eligible studies should report at least one of the following outcomes: overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and ≥3 adverse events rate (AEs). Literature screening, data extraction and quality assessment were independently conducted by two researchers. Disputes were settled by a panel of other researchers. Network meta-analysis was used to compare the efficacy and safety of various treatment regimens. Heterogeneity and consistency using the Bayesian model were evaluated in the network meta-analysis. Results: Eighteen eligible trials involving 4930 patients and 15 treatment regimens were included. Cetuximab/platinum/5-FU regimen showed higher ORR values than the following agents, including cisplatin/5-FU (odds ratio 2.96, 95% credible interval 1.42 to 6.15), cisplatin (5.43, 1.90-15.54), 5-FU (8.12, 2.22-29.61), methotrexate (8.25, 2.86-23.79), cetuximab (10.16, 1.44-71.48), and afatinib (3.64, 1.00-13.32). Immunotherapy regimens pembrolizumab/platinum/5-FU and pembrolizumab alone also showed significantly higher ORR values than these agents, while nivolumab alone showed higher ORR than the single agents. However, no significant difference was observed between Cetuximab/platinum/5-FU and pembrolizumab/platinum/5-FU. Regarding ≥3 AEs, cisplatin/paclitaxel caused the highest toxicity. No significant difference was observed on OS and PFS among all these treatment regimens. Conclusions: Cetuximab/platinum/5-FU, pembrolizumab/platinum/5-FU or pembrolizumab alone displayed high ORR with low AE rate. Nivolumab also showed better efficacy than other single agents. Although it was reported that pembrolizumab/platinum/5-FU showed better efficacy than cetuximab/platinum/5-FU, we did not find a statistically significant improvement in ORR, OS or PFS when comparing the two regimens. Therefore, further prospective trials comparing these treatment regimens remain warranted.