Camrelizumab Plus Apatinib in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma: An Open-Label, Single-Arm, Phase II Study.
Camrelizumab Plus Apatinib in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma: An Open-Label, Single-Arm, Phase II Study.
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DOI：
10.1200/jco.22.01450
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发表时间：
2023-05-10
影响因子：
45.3
通讯作者：
Chen, Ming-Yuan
中科院分区：
文献类型：
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作者：
Ding, Xi;Zhang, Wei-Jing;You, Rui;Zou, Xiong;Wang, Zhi-Qiang;Ouyang, Yan-Feng;Peng, Lan;Liu, You-Ping;Duan, Chong-Yang;Yang, Qi;Lin, Chao;Xie, Yu-Long;Chen, Si-Yuan;Liu, Yong-Long;Gu, Chen-Mei;Xie, Ruo-Qi;Huang, Pei-Yu;Hong, Ming-Huang;Hua, Yi-Jun;Chen, Ming-Yuan
据报道，免疫检查点抑制剂与抗血管生成治疗相结合具有潜在的协同抗肿瘤活性。我们观察了该方案治疗复发/转移性鼻咽癌(NPC)的有效性和安全性。这项单臂、西蒙两阶段研究招募了至少对一线系统治疗和免疫检查点抑制剂治疗无效的复发/转移性鼻咽癌患者。卡米珠单抗200 mg，每3周1次，阿帕替尼250 mg，每日1次。主要终点是客观应答率。关键的次要终点包括疾病控制率、无进展存活率、反应持续时间、总存活率和安全性。在2020年10月14日至2021年12月23日期间，58名患者入选，所有患者都进入了疗效和安全性分析集。客观有效率为65.5%(95%CI，51.9~77.5)，疾病控制率为86.2%(95%CI，74.6~93.9)。中位缓解期未达到，中位无进展生存期10.4个月(95%可信区间7.2~13.6)，中位随访期12.4个月(2.1~19.9个月)。34例(58.6%)患者发生与治疗相关的不良事件(TRAE)，其中最常见的是高血压(19.0%)、鼻咽坏死(15.5%)、头痛(12.1%)、AST升高(10.3%)和肌酸磷酸激酶升高(10.3%)。16例(27.6%)患者在进展前因无法忍受TRAE而停止阿帕替尼治疗，最常见的并发症是鼻咽坏死(9/16；56.3%)。鼻咽复发病变(优势比，5.94[95%CI，1.45~24.24])和再照射(优势比，5.33[95%CI，1.15~24.79])与鼻咽坏死呈显著正相关。Camrelzumab联合阿帕替尼对一线治疗失败的难治性复发/转移性鼻咽癌患者具有良好的抗肿瘤活性。中至重度TRAE的发生率为58.6%，包括鼻咽坏死、局部复发和有再放疗史。
Immune checkpoint inhibitors combined with antiangiogenic therapy reportedly have potential synergistic antitumor activity. We investigated the activity and safety of this regimen for recurrent/metastatic nasopharyngeal carcinoma (NPC). This single-arm, Simon two-stage study enrolled patients with recurrent/metastatic NPC who were refractory to at least first-line systemic therapy and treatment-naive to immune checkpoint inhibitors. The patients received camrelizumab 200 mg once every 3 weeks and apatinib 250 mg once per day. The primary end point was the objective response rate. Key secondary end points included disease control rate, progression-free survival, duration of response, overall survival, and safety. Between October 14, 2020, and December 23, 2021, 58 patients were enrolled, and all were included in the efficacy and safety analysis set. The objective response rate was 65.5% (95% CI, 51.9 to 77.5), and the disease control rate was 86.2% (95% CI, 74.6 to 93.9). The median duration of response was not reached, and the median progression-free survival was 10.4 months (95% CI, 7.2 to 13.6), with a median follow-up duration of 12.4 months (range, 2.1-19.9 months). Treatment-related adverse events (TRAEs) of grade 3 or higher were reported in 34 (58.6%) patients, with the most common being hypertension (19.0%), nasopharyngeal necrosis (15.5%), headache (12.1%), AST elevation (10.3%), and creatine phosphokinase elevation (10.3%). Sixteen (27.6%) patients discontinued apatinib treatment before progression because of unbearable TRAEs, and the most common complication was nasopharyngeal necrosis (9/16; 56.3%). Recurrent nasopharyngeal lesions (odds ratio, 5.94 [95% CI, 1.45 to 24.24]) and reirradiation (odds ratio, 5.33 [95% CI, 1.15 to 24.79]) were significantly positively correlated with nasopharyngeal necrosis. Camrelizumab plus apatinib had promising antitumor activity in patients with refractory recurrent/metastatic NPC who failed first-line therapy. Moderate to severe TRAEs were experienced by 58.6%, including nasopharyngeal necrosis associated with local recurrence and a history of reirradiation.