Department of Obstetrics and Gynaecology, National Clinical Research Centre for Obstetrics and Gynaecology, Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumour Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gynaecological Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
Lancet Oncol. 2024 Oct;25(10):1288-1297. doi: 10.1016/S1470-2045(24)00437-6. Epub 2024 Sep 11.
Ovarian clear cell carcinoma rarely responds to second-line chemotherapy, the recommended treatment for relapsed epithelial ovarian cancer. Here, we report the activity and safety of sintilimab in combination with bevacizumab in patients with relapsed or persistent ovarian clear cell carcinoma.
In the prospective, multicentre, single-arm, phase 2 INOVA trial, patients aged 18-75 years with histologically confirmed relapsed or persistent ovarian clear cell carcinoma were enrolled from eight tertiary hospitals in China. Eligible patients had an Eastern Cooperative Oncology Group performance status score of 0-2 and previous exposure to at least one cycle of platinum-containing chemotherapy. Enrolled patients received sintilimab (200 mg) and bevacizumab (15 mg/kg) intravenously every 3 weeks until disease progression. The primary endpoint was objective response rate assessed by independent central review based on Response Evaluation Criteria in Solid Tumours version 1.1. Eligible enrolled patients who received at least one cycle of treatment and had at least one tumour response assessment following the baseline assessment per protocol were included in the activity analysis. Patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04735861) and is ongoing.
Between April 8, 2021, and July 3, 2023, 51 patients were screened and 41 patients received at least one dose of sintilimab in combination with bevacizumab. Response evaluation was completed in 37 patients. Objective responses were observed in 15 patients (objective response rate 40·5%; 95% CI 24·8-57·9), of which five (14%) were complete responses and ten (27%) were partial responses. At data cutoff (Jan 29, 2024), the median follow-up was 16·9 months (IQR 7·5-23·4). Three (7%) patients developed grade 3 treatment-related adverse events including one patient with proteinuria, one patient with myocarditis, and one patient with rash. No treatment-related adverse events of worse than grade 3 severity were recorded. Treatment-related serious adverse events occurred in two (5%) patients including one patient with immune-related myocarditis and another with hypertension and renal dysfunction. No treatment-related deaths occurred.
Sintilimab in combination with bevacizumab showed promising anti-tumour activity and manageable safety in patients with relapsed or persistent ovarian clear cell carcinoma. Larger, randomised trials are warranted to compare this low-toxicity, chemotherapy-free combinatorial regimen with standard chemotherapy.
National Key Technology Research and Development Program of China, National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Innovent Biologics.
For the Chinese translation of the abstract see Supplementary Materials section.
卵巢透明细胞癌很少对二线化疗有反应，而二线化疗是复发性上皮性卵巢癌的推荐治疗方法。在此，我们报告了信迪利单抗联合贝伐珠单抗在复发性或持续性卵巢透明细胞癌患者中的活性和安全性。
在这项前瞻性、多中心、单臂、Ⅱ期 INOVA 试验中，从中国的 8 家三级医院招募了年龄在 18-75 岁之间、经组织学证实的复发性或持续性卵巢透明细胞癌患者。合格患者的东部肿瘤协作组体能状态评分为 0-2 分，且先前至少接受过一个周期含铂化疗。入组患者接受信迪利单抗（200mg）和贝伐珠单抗（15mg/kg）每 3 周静脉输注一次，直至疾病进展。主要终点是根据实体瘤反应评价标准 1.1 版由独立中心审查评估的客观缓解率。根据方案，对至少接受过一个周期治疗且在基线评估后至少有一次肿瘤缓解评估的合格入组患者进行疗效分析。至少接受过一次研究药物剂量的患者纳入安全性分析。该研究在 ClinicalTrials.gov 注册（NCT04735861），正在进行中。
2021 年 4 月 8 日至 2023 年 7 月 3 日，共筛选了 51 例患者，其中 41 例患者接受了信迪利单抗联合贝伐珠单抗治疗。37 例患者完成了疗效评价。在 15 例患者中观察到客观缓解（客观缓解率 40.5%；95%CI 24.8-57.9），其中 5 例（14%）为完全缓解，10 例（27%）为部分缓解。数据截止日期（2024 年 1 月 29 日）时，中位随访时间为 16.9 个月（IQR 7.5-23.4）。3 例（7%）患者发生 3 级治疗相关不良事件，包括 1 例蛋白尿、1 例心肌炎和 1 例皮疹。无 3 级以上严重程度的治疗相关不良事件发生。2 例（5%）患者发生治疗相关严重不良事件，包括 1 例免疫相关性心肌炎和另 1 例高血压和肾功能障碍。无治疗相关死亡事件发生。
信迪利单抗联合贝伐珠单抗在复发性或持续性卵巢透明细胞癌患者中显示出有前景的抗肿瘤活性和可管理的安全性。需要更大规模的随机试验来比较这种低毒性、无化疗的联合治疗方案与标准化疗。
国家重点研发计划、国家自然科学基金、北京希思科临床肿瘤学研究基金会和创新生物。
