摘要Objective:Based on the findings of the KEYNOTE-048 study,pembrolizumab in combination with platinum and fluorouracil is the standard first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma(R/M HNSCC).The efficacy and safety of pembrolizumab combined with nab-paclitaxel and platinum in such patients remain unexplored.Methods:This single-arm phase 2 study enrolled patients with R/M HNSCC who received pembrolizumab(200 mg),nab-paclitaxel(260 mg/m2),and either cisplatin(75 mg/m2)or carboplatin[area under the curve(AUC)5]every 21 d for up to six cycles,followed by pembrolizumab maintenance therapy.The primary endpoint was the objective response rate(ORR).Secondary endpoints included disease control rate(DCR),progression-free survival(PFS),duration of response(DoR),overall survival(OS),and safety.Exploratory multi-omics analyses were conducted.Results:Between April 23,2021,and August 20,2023,a total of 67 patients with R/M HNSCC were enrolled and received the study treatment.By the data cut-off date of March 2,2024,62(92.5％)patients had received cisplatin,while five(7.5％)patients had received carboplatin.The median follow-up duration was 12.7(range:2.3-34.8)months.The ORR was 62.7％,and the DCR was 88.1％.The median PFS,DoR,and OS were 9.7,13.0,and 18.7 months,respectively.The most common grade 3 adverse events(AEs)were leukopenia(22.4％)and neutropenia(28.4％).Genomic alterations correlated with efficacy outcomes,and dynamic changes in 17 plasma proteins were associated with treatment response.Upregulation of serum interferon(IFN)-y and interleukin(IL)8 levels was linked to treatment-related AEs.Conclusions:Pembrolizumab in combination with nab-paclitaxel and platinum demonstrated promising efficacy and a manageable safety profile in patients with R/M HNSCC.Future studies are warranted to confirm these findings.