帕博利珠单抗联合白蛋白结合型紫杉醇和铂类作为复发或转移性头颈部鳞状细胞癌患者一线治疗的疗效、安全性及多组学分析：一项单臂2期研究
Efficacy, safety, and multi-omics analysis of pembrolizumab combined with nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: A single-arm phase 2 study.
作者信息
Gui Lin, Chen Xinrui, Zhang Wen, Xie Zucheng, Zhang Yu, Li Weihua, Xie Tongji, Yao Jiarui, Zhu Haohua, Tang Le, Yang Jianliang, Liu Peng, Qin Yan, Zhang Changgong, He Xiaohui, Shi Yuankai
机构信息
Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
出版信息
Chin J Cancer Res. 2024 Dec 30;36(6):713-728. doi: 10.21147/j.issn.1000-9604.2024.06.09.
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)-γ 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.
目的
基于KEYNOTE-048研究的结果，帕博利珠单抗联合铂类和氟尿嘧啶是复发或转移性头颈部鳞状细胞癌（R/M HNSCC）的标准一线治疗方案。帕博利珠单抗联合白蛋白结合型紫杉醇和铂类在此类患者中的疗效和安全性仍未得到探索。
方法
这项单臂2期研究纳入了R/M HNSCC患者，他们接受帕博利珠单抗（200 mg）、白蛋白结合型紫杉醇（260 mg/m²）以及顺铂（75 mg/m²）或卡铂[曲线下面积（AUC）5]，每21天一次，共六个周期，随后进行帕博利珠单抗维持治疗。主要终点是客观缓解率（ORR）。次要终点包括疾病控制率（DCR）、无进展生存期（PFS）、缓解持续时间（DoR）、总生存期（OS）和安全性。进行了探索性多组学分析。
结果
在2021年4月23日至2023年8月20日期间，共纳入67例R/M HNSCC患者并接受了研究治疗。截至2024年3月2日的数据截止日期，62例（92.5%）患者接受了顺铂治疗，而5例（7.5%）患者接受了卡铂治疗。中位随访时间为12.7（范围：2.3 - 34.8）个月。ORR为62.7%，DCR为88.1%。中位PFS、DoR和OS分别为9.7、13.0和18.7个月。最常见的3级不良事件（AE）是白细胞减少（22.4%）和中性粒细胞减少（28.4%）。基因组改变与疗效结果相关，17种血浆蛋白的动态变化与治疗反应相关。血清干扰素（IFN）-γ和白细胞介素（IL）8水平的上调与治疗相关AE有关。
结论
帕博利珠单抗联合白蛋白结合型紫杉醇和铂类在R/M HNSCC患者中显示出有前景的疗效和可管理的安全性。未来有必要进行研究以证实这些发现。
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