Camrelizumab plus apatinib in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia (CAP 01): a single-arm, open-label, phase 2 trial
Camrelizumab plus apatinib in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia (CAP 01): a single-arm, open-label, phase 2 trial
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DOI：
10.1016/s1470-2045(21)00460-5
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发表时间：
2021-11-01
期刊：
影响因子：
51.1
通讯作者：
Xiang, Yang
中科院分区：
文献类型：
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作者：
Cheng, Hongyan;Zong, Liju;Xiang, Yang
背景：高风险化疗难治性或复发的妊娠滋养细胞瘤患者的治疗选择很少。免疫治疗和抗血管生成药物的协同抗肿瘤作用已在许多实体肿瘤中得到证实。这项2期试验评估了camrelizumab （PD-1抑制剂）和apatinib （VEGF受体抑制剂）在高危化疗难治性或复发性妊娠滋养细胞瘤患者中的活性和安全性。方法：这是一项单臂、开放标签、2期试验，在中国北京的一家三级卫生保健中心进行。高危（国际妇产科联合会评分>= 7）化疗难治性或复发的妊娠滋养细胞瘤患者（18-70岁），既往至少接受过2线以上不成功的多药化疗方案，东部肿瘤合作组评分0-2分，符合纳入条件。患者接受4周周期的静脉注射camrelizumab 200mg，每2周加口服阿帕替尼250mg，每天1次，直到疾病进展或不可接受的毒性。主要终点是根据血清人绒毛膜促性腺激素浓度评估客观缓解率。对所有接受至少一剂研究药物的患者的活性和安全性进行了分析。研究仍在进行中，但招募已经完成。该研究已在ClinicalTrials.gov注册，编号NCT04047017。在2019年8月7日至2020年3月18日期间，20名患者入组；19例（95%）被诊断为绒毛膜癌，1例（5%）被诊断为胎盘部位滋养细胞瘤。中位随访时间为18middot5个月（IQR 14middot6-20middot9）。客观有效率为55% (95% CI 32-77)；10例（50%;95% CI 27-73）患者完全缓解。最常见的3级治疗相关不良事件是高血压（5例[25%]患者）、皮疹（4例[20%]患者）、中性粒细胞减少（2例[10%]）、白细胞减少（2例[10%]）和天冬氨酸氨基转移酶升高（2例[10%]）。1例出现治疗相关严重不良事件（天冬氨酸转氨酶高于正常上限19倍）。没有4级或5级治疗相关不良事件的报道。Camrelizumab联合阿帕替尼显示出有希望的抗肿瘤活性和可接受的毒性，可能是治疗高风险化疗难治性或复发的妊娠滋养细胞肿瘤的一种补救性治疗选择。免疫检查点抑制剂联合化疗用于重度治疗的患者，以及camrelizumab + apatinib用于高危妊娠滋养细胞瘤患者的2期试验正在研究中。国家自然科学基金资助，江苏恒瑞制药。Elsevier Ltd.版权所有版权所有。
Background Treatment options for patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia are scarce. The synergistic antitumour effect of immunotherapy and antiangiogenic drugs has been shown in many solid tumours. This phase 2 trial evaluated the activity and safety of camrelizumab (PD-1 inhibitor) plus apatinib (VEGF receptor inhibitor) in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia. Methods This was a single-arm, open-label, phase 2 trial, done at a single tertiary health-care centre in Beijing, China. Women (18-70 years) with high-risk (International Federation of Gynecology and Obstetrics score >= 7) chemorefractory or relapsed gestational trophoblastic neoplasia who had received at least two lines of previously unsuccessful multidrug chemotherapy regimens and had an Eastern Cooperative Oncology Group performance status of 0-2 were eligible for inclusion. Patients received 4-week cycles of intravenous camrelizumab 200 mg every 2 weeks plus oral apatinib 250 mg once per day until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed according to serum human chorionic gonadotrophin concentration. Activity and safety were analysed in all patients who received at least one dose of study drug. The study is ongoing, but recruitment is complete. The study is registered with ClinicalTrials.gov, NCT04047017. Findings Between Aug 7, 2019, and March 18, 2020, 20 patients enrolled; 19 (95%) were diagnosed with choriocarcinoma and one (5%) had placental site trophoblastic tumour. The median follow-up duration was 18middot5 months (IQR 14middot6-20middot9). The objective response rate was 55% (95% CI 32-77); ten (50%; 95% CI 27-73) patients had complete response. The most common grade 3 treatment-related adverse events were hypertension (five [25%] patients), rash (four [20%] patients), neutropenia (two [10%]), leukocytopenia (two [10%]), and aspartate amino transferase increase (two [10%]). One patient had a treatment-related serious adverse event (aspartate aminotransferase 19-times higher than the upper limit of normal). No grade 4 or 5 treatment-related adverse events were reported. Interpretation Camrelizumab plus apatinib showed promising antitumour activity and acceptable toxicity and could be a salvage therapy option for the treatment of high-risk chemorefractory or relapsed gestational trophoblastic neoplasia. Immune checkpoint inhibitors combined with chemotherapy for heavily-treated patients and upfront use of camrelizumab plus apatinib for patients with high-risk gestational trophoblastic neoplasia are under investigation in phase 2 trials. Funding National Natural Science Foundation of China, Jiangsu Hengrui Pharmaceuticals. Copyright (c) 2021 Elsevier Ltd. All rights reserved.