Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, 200032, China.
Mol Cancer. 2024 Aug 9;23(1):162. doi: 10.1186/s12943-024-02076-x.
Platinum-resistant or refractory ovarian cancer is a highly lethal gynecologic disease with limited treatment options. Chiauranib is a novel small-molecule selective inhibitor, which could effectively target multiple pathways including Aurora B and CSF-1R to inhibit cell cycle process and improve anti-tumor immune function, as long as VEGF pathway for tumor extinction.
A phase II study was sequentially conducted after a phase Ib monotherapy study to evaluate the efficacy of chiauranib combined with chemotherapy. Chinese patients with recurrent ovarian cancer were enrolled. Eligible patients received chiauranib combined with a maximum of six cycles of chemotherapy: etoposide (CE group) or weekly-paclitaxel (CP group). Patients, who exhibited a complete or partial response, or stable disease following combo treatment, progressed to maintenance phase to receive chiauranib monotherapy. Primary endpoint was progression-free survival (PFS) according to RECIST v1.1.
From November 2017 to March 2019, 25 patients were enrolled in a phase 1b study and a median PFS of 3.7 months (95% CI 1.8-NE) was achieved by chiauranib monotherapy. From July 2019 to December 2020, a total of 47 patients were enrolled in the phase II study. One CP patient did not receive the study drugs, and three patients withdrew before the first tumor assessment. Thus, 43 patients (CE group: 22 patients; CP group: 21 patients) were included in the evaluation. The median PFS was 5·4 months (95% CI 2·8-5·6) and 5·6 months (95% CI 3·4-7·0), respectively.
This was the first study to evaluate chiauranib, a novel multi-targeted kinase inhibitor in patients with ovarian cancer. The administration of chiauranib along with etoposide or weekly-paclitaxel significantly enhanced the efficacy with manageable adverse events. This warrants further clinical studies on this novel treatment. A phase III study is promising and ongoing.
ClinicaTrials.gov identifier: NCT03901118 (phase II) and NCT03166891 (phase Ib).
铂耐药或难治性卵巢癌是一种高度致命的妇科疾病，治疗选择有限。恰拉尼布是一种新型小分子选择性抑制剂，可有效靶向包括 Aurora B 和 CSF-1R 在内的多种途径，抑制细胞周期过程并改善抗肿瘤免疫功能，同时针对肿瘤的 VEGF 通路进行治疗。
在一项单药治疗的 I 期研究之后，进行了一项 II 期研究，以评估恰拉尼布联合化疗的疗效。中国复发性卵巢癌患者入组。符合条件的患者接受恰拉尼布联合最多 6 个周期的化疗：依托泊苷（CE 组）或每周紫杉醇（CP 组）。联合治疗后出现完全或部分缓解或疾病稳定的患者进展至维持阶段，接受恰拉尼布单药治疗。主要终点为根据 RECIST v1.1 评估的无进展生存期（PFS）。
从 2017 年 11 月到 2019 年 3 月，25 例患者入组了 I 期研究，恰拉尼布单药治疗的中位 PFS 为 3.7 个月（95%CI 1.8-NE）。从 2019 年 7 月到 2020 年 12 月，共有 47 例患者入组了 II 期研究。1 例 CP 患者未接受研究药物，3 例患者在首次肿瘤评估前退出。因此，43 例患者（CE 组：22 例；CP 组：21 例）被纳入评估。中位 PFS 分别为 5.4 个月（95%CI 2.8-5.6）和 5.6 个月（95%CI 3.4-7.0）。
这是第一项评估恰拉尼布（一种新型多靶点激酶抑制剂）在卵巢癌患者中的研究。恰拉尼布联合依托泊苷或每周紫杉醇治疗显著提高了疗效，且不良反应可管理。这为这种新型治疗方法的进一步临床研究提供了依据。一项 III 期研究正在进行中，前景广阔。
ClinicalTrials.gov 标识符：NCT03901118（II 期）和 NCT03166891（I 期）。
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