Department of Obstetrics and Gynecology, National Clinical Research Centre for Obstetric and Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Obstetrics and Gynecology, National Clinical Research Centre for Obstetric and Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Lancet Oncol. 2021 Nov;22(11):1609-1617. doi: 10.1016/S1470-2045(21)00460-5. Epub 2021 Oct 5.
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.
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.
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 18·5 months (IQR 14·6-20·9). 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 aminotransferase 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.
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.
National Natural Science Foundation of China, Jiangsu Hengrui Pharmaceuticals.
对于高危化疗耐药或复发妊娠滋养细胞肿瘤患者，治疗选择有限。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瘤中得到证实。这项 2 期试验评估了卡瑞利珠单抗（PD-1 抑制剂）联合阿帕替尼（VEGF 受体抑制剂）在高危化疗耐药或复发妊娠滋养细胞肿瘤患者中的活性和安全性。
这是一项在中国北京一家三级医疗中心进行的单臂、开放标签、2 期试验。入组标准为接受至少两线先前不成功的多药化疗方案且 Eastern Cooperative Oncology Group 体能状态为 0-2 的高危（国际妇产科联合会评分≥7）化疗耐药或复发妊娠滋养细胞肿瘤患者（18-70 岁）。患者接受静脉注射卡瑞利珠单抗 200mg，每 2 周 1 次，联合口服阿帕替尼 250mg，每日 1 次，直至疾病进展或出现不可接受的毒性。主要终点为根据血清人绒毛膜促性腺激素浓度评估的客观缓解率。对至少接受 1 剂研究药物的所有患者进行疗效和安全性分析。该研究正在进行中，但已完成招募。该研究在 ClinicalTrials.gov 注册，编号为 NCT04047017。
2019 年 8 月 7 日至 2020 年 3 月 18 日期间，共纳入 20 例患者；19 例（95%）患者诊断为绒癌，1 例（5%）患者诊断为胎盘部位滋养细胞肿瘤。中位随访时间为 18.5 个月（IQR 14.6-20.9）。客观缓解率为 55%（95%CI 32-77）；10 例（50%）患者达到完全缓解。最常见的 3 级治疗相关不良事件为高血压（5 例[25%]）、皮疹（4 例[20%]）、中性粒细胞减少症（2 例[10%]）、白细胞减少症（2 例[10%]）和天门冬氨酸氨基转移酶升高（2 例[10%]）。1 例患者出现与治疗相关的严重不良事件（天门冬氨酸氨基转移酶比正常值高 19 倍）。未报告 4 级或 5 级治疗相关不良事件。
卡瑞利珠单抗联合阿帕替尼显示出有前景的抗肿瘤活性和可接受的毒性，可能成为高危化疗耐药或复发妊娠滋养细胞肿瘤的一种挽救性治疗选择。免疫检查点抑制剂联合化疗治疗经大量治疗的患者，以及卡瑞利珠单抗联合阿帕替尼用于高危妊娠滋养细胞肿瘤患者的一线治疗，正在进行 2 期临床试验。
国家自然科学基金，江苏恒瑞医药。
