脂质体伊立替康联合尼妥珠单抗治疗免疫检查点抑制剂难治性复发或转移性鼻咽癌的疗效与安全性：一项单臂、开放标签、II期试验
Efficacy and safety of liposomal irinotecan plus nimotuzumab in immune checkpoint inhibitor-refractory recurrent or metastatic nasopharyngeal carcinoma: a single-arm, open-label, phase II trial.
文献信息
| PMID | 42729623 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Shuiqing He |
| 作者单位 | 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, 510060, Guangzhou, China. |
| 期刊 | EClinicalMedicine |
| SCI 分区 | Q1 |
| IF | 11.8 |
| 研究类型 | 临床研究 · 临床 |
| 所属专科 | 鼻咽癌 |
中文摘要
背景： 在接受免疫检查点抑制剂（ICI）治疗后进展的复发或转移性鼻咽癌（R/M NPC）患者治疗选择有限且预后不良。我们评估了脂质体伊立替康联合尼妥珠单抗在表皮生长因子受体（EGFR）阳性、ICI难治性R/M NPC患者中的疗效和安全性。
方法： 在这项在中国进行的单臂、开放标签、II期试验（NCT06414577）中，于2024年5月27日至2025年1月9日期间入组了EGFR阳性、ICI难治性R/M NPC患者。患者接受静脉注射脂质体伊立替康（70 mg/m2）联合尼妥珠单抗（400 mg），每2周一次，最多八个周期。主要终点是根据实体瘤疗效评价标准1.1版评估的客观缓解率（ORR）。
结果： 共入组36例经重度治疗的患者，其中12例（33.3%）既往接受过三线或以上针对晚期疾病的治疗。在意向治疗人群中，36例患者中有13例达到客观缓解（ORR 36.1%；95% CI 20.8-53.8），36例中有22例达到疾病控制（61.1%）。中位无进展生存期为3.0个月（95% CI，2.2-4.1），中位缓解持续时间为2.3个月（95% CI 1.5-3.1）。中位随访22.0个月后，中位总生存期为14.1个月（95% CI，8.7-不可估计）。36例患者中有8例（22.2%）发生3级或以上治疗相关不良事件，未观察到治疗相关死亡。在一项事后探索性分析中，血浆EB病毒DNA早期下降至少50%与更高的ORR相关。
结论： 脂质体伊立替康联合尼妥珠单抗在经重度治疗的ICI难治性R/M NPC患者中显示出初步抗肿瘤活性和可控的安全性。然而，缓解持久性有限，需要进一步的比较研究来评估其临床价值并识别最可能获得持久获益的患者。
资助： 本研究得到国家自然科学基金、广东省食管癌研究所科技计划项目和中国博士后科学基金的资助。
英文摘要
BACKGROUND: Patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) who progress after immune checkpoint inhibitor (ICI) therapy have limited treatment options and poor outcomes. We evaluated the efficacy and safety of liposomal irinotecan plus nimotuzumab in patients with epidermal growth factor receptor (EGFR)-positive, ICI-refractory R/M NPC.
METHODS: In this single-arm, open-label, phase II trial (NCT06414577) conducted in China, patients with EGFR-positive, ICI-refractory R/M NPC were enrolled between May 27, 2024, and January 9, 2025. Patients received intravenous liposomal irinotecan (70 mg/m2) plus nimotuzumab (400 mg) every 2 weeks for up to eight cycles. The primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1.
FINDINGS: Thirty-six heavily pretreated patients were enrolled, of whom 12 (33.3%) had received three or more prior lines of therapy for advanced disease. In the intention-to-treat population, 13 of 36 patients achieved an objective response (ORR 36.1%; 95% CI 20.8-53.8), and 22 of 36 patients achieved disease control (61.1%). Median progression-free survival was 3.0 months (95% CI, 2.2-4.1), and median duration of response was 2.3 months (95% CI 1.5-3.1). After a median follow-up of 22.0 months, the median overall survival was 14.1 months (95% CI, 8.7-not estimable). Grade 3 or higher treatment-related adverse events occurred in eight of 36 patients (22.2%), and no treatment-related deaths were observed. In a post-hoc exploratory analysis, an early decline of at least 50% in plasma Epstein-Barr virus DNA was associated with a higher ORR.
INTERPRETATION: Liposomal irinotecan plus nimotuzumab showed preliminary antitumor activity and manageable safety in heavily pretreated patients with ICI-refractory R/M NPC. However, response durability was limited, and further comparative studies are needed to evaluate its clinical value and identify patients most likely to derive durable benefit.
FUNDING: Supported by grants from the National Natural Science Foundation of China, Science and Technology Program of Guangdong Esophageal Cancer Institute, and China Postdoctoral Science Foundation.