Efficacy and safety of chiauranib in a combination therapy in platinum-resistant or refractory ovarian cancer: a multicenter, open-label, phase Ib and II study

IF 27.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2024-08-09 DOI:10.1186/s12943-024-02076-x

Jin Li, Jihong Liu, Rutie Yin, Dongling Zou, Hong Zheng, Junning Cao, Zhendong Chen, Wei Sun, Yunong Gao, Songling Zhang, Linjuan Zeng, Ruifang An, Xianping Lu, Shuang Ye, Xiaohua Wu

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引用次数: 0

Abstract

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).

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巧拉尼联合疗法治疗铂类耐药或难治性卵巢癌的疗效和安全性：一项多中心、开放标签、Ib 期和 II 期研究

铂耐药或难治性卵巢癌是一种致死率极高的妇科疾病，但治疗方案却十分有限。Chiauranib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在内的多条通路，抑制细胞周期过程，提高抗肿瘤免疫功能，同时也可靶向VEGF通路消灭肿瘤。在Ib期单药治疗研究之后，我们又进行了一项II期研究，以评估chiauranib联合化疗的疗效。研究招募了中国复发性卵巢癌患者。符合条件的患者接受巧拉尼联合化疗，最多6个周期：依托泊苷（CE组）或每周紫杉醇（CP组）。如果患者在联合治疗后出现完全或部分应答，或病情稳定，则进入维持治疗阶段，接受chiauranib单药治疗。根据RECIST v1.1标准，主要终点为无进展生存期（PFS）。2017年11月至2019年3月，25名患者入组1b期研究，接受chiauranib单药治疗的中位PFS为3.7个月（95% CI 1.8-NE）。2019年7月至2020年12月，共有47名患者入组II期研究。一名 CP 患者未接受研究药物，三名患者在首次肿瘤评估前退出。因此，43 名患者（CE 组：22 名患者；CP 组：21 名患者）被纳入评估。中位生存期分别为 5-4 个月（95% CI 2-8-5-6 ）和 5-6 个月（95% CI 3-4-7-0）。这是第一项评估卵巢癌患者使用新型多靶点激酶抑制剂chiauranib的研究。chiauranib与依托泊苷或每周紫杉醇合用可显著提高疗效，且不良反应可控。因此，有必要对这种新型疗法进行进一步的临床研究。目前正在进行的III期研究前景广阔。ClinicaTrials.gov 标识符：NCT03901118（II 期）和 NCT03166891（Ib 期）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

期刊介绍： Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.