Lu Nian, Jiang Yao-Fei, Xia Wei-Xiong, Huang Ying, Xie Chuan-Miao, Xu Cheng, Ye Yan-Fang, Liu Guo-Ying, Bei Wei-Xin, Ke Liang-Ru, Li Wang-Zhong, Zhang Cheng, Wang Xin, Liu Qin, Chen Xi, Chen Zi-Xiong, Xie Changqing, Liang Hu, Xiang Yan-Qun
Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China.
Department of Radiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China.
EClinicalMedicine. 2023 Aug 4;62:102136. doi: 10.1016/j.eclinm.2023.102136. eCollection 2023 Aug.
There are limited treatment options for patients with metastatic nasopharyngeal carcinoma (mNPC) after failure of platinum-based chemotherapy. In this trial, we assessed the efficacy and safety of sintilimab plus bevacizumab in patients with mNPC where platinum-based chemotherapy has been ineffective.
This was a single-centre, open-label, single-arm, phase 2 trial in Guangzhou, China for patients with mNPC progressed after at least one line of systemic therapy. Eligible patients were between 18 and 75 years old, were histologically confirmed differentiated or undifferentiated non-keratinized NPC, were ineffective after platinum-based chemotherapy, and they had at least one measurable metastatic lesion assessed with Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V.1.1) by investigators and unsuitable for local surgery or radiotherapy. Key exclusion criterion was previous treatment with anti-PD-1/PD-L1 antibodies plus anti-VEGF antibodies and high risk of hemorrhage or nasopharyngeal necrosis. Patients were enrolled and received sintilimab (200 mg) plus bevacizumab (7.5 mg/kg) intravenously every 3 weeks. Intention-to-treat population was included in primary endpoint analyses and safety analyses. The primary endpoint was objective response rate (ORR) assessed by investigators following the guidelines of RECIST V1.1. Key secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. This trial is registered with ClinicalTrials.gov (NCT04872582).
Between July 29, 2021 and August 16, 2022, 33 patients were enrolled. Median age was 46 years (range, 18-64 years), and 63.6% of patients had previously received two or more lines of chemotherapy for metastatic disease. Median follow-up was 7.6 months (range, 4.1-17.5 months). ORR was 54.5% (95% CI, 36.4-71.9%) with 3 complete responses (9.1%) and 15 partial responses (45.5%). Median PFS was 6.8 months (95% CI, 5.2 months to not estimable). Median DOR was 7.2 months (95% CI, 4.4 months to not estimable). Median OS was not reached. The most common potential immune-related adverse event (AE) was Grade 1-2 hypothyroidism (42.4%). Treatment-related grade 3 or 4 AEs occurred in 7 patients (21.2%), including nasal necrosis (3/33), hypertension (1/33), pruritus (1/33), total bilirubin increased (1/33) and anaphylactic shock (1/33). No treatment-related deaths and severe epistaxis occurred.
This phase 2 trial showed that sintilimab plus bevacizumab demonstrated promising antitumour activity and manageable toxicities in patients with mNPC after failure of platinum-based chemotherapy. Further trials are warranted, and the detailed mechanisms need to be elucidated.
The Guangdong Basic and Applied Basic Research Foundation, the National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province, and the Science and Technology Planning Project of International Cooperation of Guangdong Province.
对于铂类化疗失败后的转移性鼻咽癌（mNPC）患者，治疗选择有限。在本试验中，我们评估了信迪利单抗联合贝伐珠单抗在铂类化疗无效的mNPC患者中的疗效和安全性。
这是一项在中国广州开展的单中心、开放标签、单臂2期试验，针对至少经过一线全身治疗后病情进展的mNPC患者。符合条件的患者年龄在18至75岁之间，经组织学确诊为分化或未分化的非角化型鼻咽癌，铂类化疗无效，且经研究者根据实体瘤疗效评价标准第1.1版（RECIST V.1.1）评估至少有一处可测量的转移病灶，不适合局部手术或放疗。主要排除标准是既往接受过抗PD-1/PD-L1抗体联合抗VEGF抗体治疗以及有出血或鼻咽坏死的高风险。患者入组并接受信迪利单抗（200mg）联合贝伐珠单抗（7.5mg/kg）静脉注射，每3周一次。意向性治疗人群纳入主要终点分析和安全性分析。主要终点是研究者根据RECIST V1.1指南评估的客观缓解率（ORR）。关键次要终点是无进展生存期（PFS）、总生存期（OS）、缓解持续时间（DOR）和安全性。本试验已在ClinicalTrials.gov注册（NCT04872582）。
在2021年7月29日至2022年8月16日期间，共入组33例患者。中位年龄为46岁（范围18 - 64岁），63.6%的患者既往因转移性疾病接受过两线或更多线化疗。中位随访时间为7.6个月（范围4.1 - 17.5个月）。ORR为54.5%（95%CI，36.4 - 71.9%），有3例完全缓解（9.1%）和15例部分缓解（45.5%）。中位PFS为6.8个月（95%CI，5.2个月至无法估计）。中位DOR为7.2个月（95%CI，4.4个月至无法估计）。中位OS未达到。最常见的潜在免疫相关不良事件（AE）是1 - 2级甲状腺功能减退（42.4%）。7例患者（21.2%）发生了与治疗相关的3级或4级AE，包括鼻坏死（3/33）、高血压（1/33）、瘙痒（1/33）、总胆红素升高（1/33）和过敏性休克（1/33）。未发生与治疗相关的死亡和严重鼻出血。
这项2期试验表明，信迪利单抗联合贝伐珠单抗在铂类化疗失败的mNPC患者中显示出有前景的抗肿瘤活性和可管理的毒性。有必要进行进一步试验，并阐明详细机制。
广东省基础与应用基础研究基金、国家自然科学基金、广东省自然科学基金、广东省国际合作科技计划项目。
