Fruquintinib Plus Sintilimab in Patients with Treatment-Naive and Previously Treated Advanced Renal Cell Carcinoma: Results from a Phase Ib/II Clinical Trial.

IF 4.4 3区 医学 Q2 ONCOLOGY
Targeted Oncology Pub Date : 2025-01-01 Epub Date: 2025-01-13 DOI:10.1007/s11523-024-01120-6
Hua Xu, Xin Yao, Zhisong He, Hong Luo, Guiling Li, Jianming Guo, Lei Diao, Yu Fan, Yuan Li, Jiquan Fan, Xiaoyi Hu, Puhan Lu, Haiyan Shi, Keyan Chen, Panfeng Tan, Songhua Fan, Michael Shi, Weiguo Su, Dingwei Ye
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引用次数: 0

Abstract

Background: Antiangiogenic inhibitors plus immune checkpoint inhibitors have synergistic antitumor activity and have improved treatment outcomes in patients with renal cell carcinoma (RCC).

Objective: We report the RCC cohort from a phase Ib/II study in Chinese patients evaluating the efficacy and safety of fruquintinib plus sintilimab in treating advanced clear cell RCC (ccRCC).

Patients and methods: Eligible patients had pathologically confirmed advanced ccRCC. Patients received fruquintinib 5 mg once daily, 2 weeks on/1 week off, plus sintilimab 200 mg every 3 weeks in 3-week cycles. The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1.

Results: By March 31, 2023, 42 patients (median age 58.9 years; 81.0% male) had been treated in the RCC cohort. Among treatment-naive patients (n = 22), confirmed ORR was 68.2% (95% confidence interval [CI] 45.1-86.1). The median progression-free survival (PFS) was not reached, and 18-month PFS rate was 59.4%. Among previously treated patients (n = 20), the confirmed ORR was 60.0% (95% CI 36.1-80.9), and the median PFS was 15.9 (95% CI 5.4-19.3) months. All patients had adverse events related to study treatment, 52.4% of which were grade ≥ 3 in severity. Treatment-related adverse events with an incidence of ≥ 40% included proteinuria, hypothyroidism, hypercholesterolemia, hypertriglyceridemia, and hypoalbuminemia.

Conclusions: Fruquintinib plus sintilimab demonstrated promising efficacy in advanced ccRCC and was well tolerated. A phase III study (FRUSICA-02) using this combination regimen in patients with previously treated advanced ccRCC is ongoing.

Trial registration number: The study was registered with ClinicalTrials.gov (NCT03903705).

对治疗无效和既往接受过治疗的晚期肾细胞癌患者使用 Fruquintinib 加 Sintilimab 的 Ib/II 期临床试验结果:Ib/II期临床试验结果。
背景:抗血管生成抑制剂与免疫检查点抑制剂具有协同抗肿瘤活性,并改善肾细胞癌(RCC)患者的治疗效果。目的:我们报道来自中国患者Ib/II期研究的RCC队列,评估fruquininib + sintilmab治疗晚期透明细胞RCC (ccRCC)的有效性和安全性。患者和方法:符合条件的患者病理证实为晚期ccRCC。患者接受fruquininib 5mg,每日1次,2周开/1周停,加上sintilmab 200mg,每3周一次,3周一个周期。主要终点是研究者根据实体肿瘤反应评估标准1.1版评估的客观缓解率(ORR)。结果:截至2023年3月31日,42例患者(中位年龄58.9岁;在RCC队列中接受过治疗(81.0%为男性)。在未接受治疗的患者(n = 22)中,确诊的ORR为68.2%(95%可信区间[CI] 45.1-86.1)。中位无进展生存期(PFS)未达到,18个月PFS率为59.4%。在先前接受治疗的患者(n = 20)中,确诊的ORR为60.0% (95% CI 36.1-80.9),中位PFS为15.9个月(95% CI 5.4-19.3)。所有患者均发生与研究治疗相关的不良事件,其中52.4%的不良事件严重程度≥3级。发生率≥40%的治疗相关不良事件包括蛋白尿、甲状腺功能减退、高胆固醇血症、高甘油三酯血症和低白蛋白血症。结论:氟喹替尼联合辛替单抗治疗晚期ccRCC疗效良好,耐受性良好。一项在先前治疗过的晚期ccRCC患者中使用该联合方案的III期研究(FRUSICA-02)正在进行中。试验注册号:该研究已在ClinicalTrials.gov注册(NCT03903705)。
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来源期刊
Targeted Oncology
Targeted Oncology 医学-肿瘤学
CiteScore
8.40
自引率
3.70%
发文量
64
审稿时长
>12 weeks
期刊介绍: Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes: Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches. Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways. Current Opinion articles that place interesting areas in perspective. Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations. Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement. Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.
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