The Optimal Second-Line Systemic Treatment Model For Recurrent And/or Metastatic Head And Neck Squamous Cell Carcinoma:a Bayesian Network Meta-Analysis

Background:Head and neck squamous cell carcinoma(HNSCC),originating from the epithelial tissue of the head and neck region,mainly includes oral cancer,oropharyngeal cancer,hypopharyngeal cancer and laryngeal cancer.As estimated by the International Agency for Research of Cancer,there were approximately 830,000 patients newly diagnosed with HNSCC worldwide in 2018,and about 430,000 patients died of this type of tumor throughout the year.Approximately 4% ～ 26% of patients present with metastatic disease at the first diagnosis,and among patients who have not been diagnosed with metastasis,despite radical treatment,more than 30%will eventually develop recurrent and/or metastatic(R/M)diseases.Treatment options for R/M HNSCC are limited,especially in regard to second-line regimens,mainly referring to chemotherapy,targeted therapy or a combination of the two.The advent of immunotherapy has led to survival hope for patients with metastatic tumors in recent years.However,its application is controversial in the administration of different immune checkpoint inhibitors(ICIs)in second-line treatment of R/M HNSCC.Further determination of the exact role immunotherapy plays in second-line treatment is imperative.Objective:The optimal second-line systemic treatment model for R/M HNSCC remains controversial.A Bayesian network meta-analysis(NMA)was performed to address this issue with regard to efficacy and toxicity.Methods:By searching MEDLINE(via Pub Med),Embase,the Cochrane Central Register of Controlled Trials and Web of Science,eligible studies were extracted.Efficacy,represented as overall survival(OS)and progression-free survival(PFS),and overall toxicity,represented as ≥ grade 3 severe acute events(sAE),were assessed to compare the following 7 treatment models through a NMA: standard-of-care therapy(SoC),single targeted therapy different from SoC(ST),double targeted therapy(DT),targeted therapy combined with chemotherapy(T + C),single immune checkpoint inhibitor therapy(SI),double immune checkpoint inhibitor therapy(DI)and single chemotherapy different from SoC(SC).Rank probabilities according to the values of the surface under the cumulative ranking curve(SUCRA)were separately determined for efficacy and toxicity.Results:In total,5285 patients from 24 eligible studies were finally screened,with 5184,4532 and 4026 involved in the NMA of OS,PFS and s AE,respectively.In terms of OS,SI was superior to the other treatments,followed by DI,ST,T + C,SoC,DT and SC.Other than SI and SC,all treatments tended to be consistent,with hazard ratios(HRs)close to 1 between groups.For PFS,ST ranked first,while DT ranked last.For the toxicity profiles,compared with the other models,SI resulted in the lowest incidences of s AE,with statistical significance over SoC(odds ratio [OR] 0.31,95%credible interval [CrI] 0.11 to 0.90),ST(OR 0.23,95% CrI 0.06 to 0.86)and DT(OR0.11,95% CrI 0.02 to 0.53),while DT was the worst of all.Combining the SUCRA values of OS and s AE,a cluster plot illustrated the superiority of SI,which demonstrated the best OS and tolerability toward s AE.Conclusion:This NMA,encompassing 5285 individuals from 24 trials,revealed that compared with SoC,ST,DT,T + C,DI and SC,SI achieved the best OS as well as the least s AE.SI may thus serve as the optimal second-line systemic treatment model for R/M HNSCC.