抗表皮生长因子受体（EGFR）单克隆抗体联合顺铂和 5-氟尿嘧啶治疗根治性放疗后转移性鼻咽癌患者的多中心、开放标签、II 期临床试验。

Anti-epidermal growth factor receptor (EGFR) monoclonal antibody combined with cisplatin and 5-fluorouracil in patients with metastatic nasopharyngeal carcinoma after radical radiotherapy: a multicentre, open-label, phase II clinical trial.

机构信息

Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Centre, Zhongnan Hospital of Wuhan University, Wuhan; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation centre of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou.

Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation centre of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou.

出版信息

Ann Oncol. 2019 Apr 1;30(4):637-643. doi: 10.1093/annonc/mdz020.

DOI:10.1093/annonc/mdz020

PMID:30689735

Abstract

BACKGROUND

We conducted a single-arm phase II trial to evaluate the efficacy and adverse effects (AEs) of an anti-epidermal growth factor receptor monoclonal antibody, nimotuzumab, combined with cisplatin and 5-fluorouracil (PF) as first-line treatment in recurrent metastatic nasopharyngeal carcinoma after radical radiotherapy.

METHODS

Patients who met the eligibility criteria were recruited from ten institutions (ClinicalTrials.gov; NCT01616849). A Simon optimal two-stage design was used to calculate the sample size. All patients received weekly nimotuzumab (200 mg) added to cisplatin (100 mg/m2 D1) and 5-fluorouracil (4 g/m2 continuous infusion D1-4) every 3-weekly for a maximum of six cycles. Primary end point was objective response rate (ORR). Secondary end points included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and AEs.

RESULTS

A total of 35 patients were enrolled (13 in stage 1 and 22 in stage 2). Overall ORR and DCR were 71.4% (25/35) and 85.7% (30/35), respectively. Median PFS and OS were 7.0 (95% CI 5.8-8.2) months and 16.3 (95% CI 11.4-21.3) months, respectively. Unplanned exploratory analyses suggest that patients who received ≥2400 mg nimotuzumab and ≥4 cycles of PF had superior ORR, PFS and OS than those who did not (88.9% versus 12.5%, P < 0.001; 7.4 versus 2.7 months, P = 0.081; 17.0 versus 8.0 months, P = 0.202). Favourable subgroups included patients with lung metastasis [HROS 0.324 (95% CI 0.146-0.717), P = 0.008] and disease-free interval of >12 months [HROS 0.307 (95% CI 0.131-0.724), P = 0.004], but no difference was observed for metastatic burden. The only major grade 3/4 AE was leukopenia (62.9%).

CONCLUSION

Combination nimotuzumab-PF chemotherapy demonstrates potential efficacy, and is well tolerated as first-line chemotherapy regimen in recurrent metastatic nasopharyngeal carcinoma.

摘要

背景

我们进行了一项单臂 II 期临床试验，以评估抗表皮生长因子受体单克隆抗体尼妥珠单抗联合顺铂和 5-氟尿嘧啶（PF）作为根治性放疗后复发转移性鼻咽癌的一线治疗的疗效和不良反应（AE）。

方法

从十个机构（ClinicalTrials.gov；NCT01616849）招募符合入选标准的患者。采用 Simon 最优两阶段设计计算样本量。所有患者接受每周尼妥珠单抗（200mg）联合顺铂（100mg/m2，D1）和 5-氟尿嘧啶（4g/m2 持续输注，D1-4）治疗，每 3 周为一个周期，最多 6 个周期。主要终点为客观缓解率（ORR）。次要终点包括疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）和 AE。

结果

共纳入 35 例患者（1 期 13 例，2 期 22 例）。总 ORR 和 DCR 分别为 71.4%（25/35）和 85.7%（30/35）。中位 PFS 和 OS 分别为 7.0（95%CI 5.8-8.2）个月和 16.3（95%CI 11.4-21.3）个月。未计划的探索性分析表明，接受≥2400mg 尼妥珠单抗和≥4 个周期 PF 的患者 ORR、PFS 和 OS 优于未接受的患者（88.9%比 12.5%，P<0.001；7.4 比 2.7 个月，P=0.081；17.0 比 8.0 个月，P=0.202）。有利的亚组包括肺转移患者[HR 0.324（95%CI 0.146-0.717），P=0.008]和无疾病间隔时间>12 个月的患者[HR 0.307（95%CI 0.131-0.724），P=0.004]，但转移负荷无差异。唯一的主要 3/4 级 AE 是白细胞减少症（62.9%）。