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 carcino...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/m^(2)),and either cisplatin(75 mg/m^(2))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(Do R),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,Do R,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)-γand interleukin(IL)8levels 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.展开更多
基金supported by the China National Major Project for New Drug Innovation(No.2017ZX09304015)the Beijing Hope Run Special Fund of the Cancer Foundation of China(No.LC2022A30)the Beijing Vlove Charity Foundation(No.JYKY2024-0200616033)。
文摘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/m^(2)),and either cisplatin(75 mg/m^(2))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(Do R),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,Do R,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)-γand interleukin(IL)8levels 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.
