Randomized phase II dose comparison LITESPARK-013 study of belzutifan in patients with advanced clear cell renal cell carcinoma.

IF 56.7 1区医学 Q1 ONCOLOGY Annals of Oncology Pub Date : 2024-09-02 DOI:10.1016/j.annonc.2024.08.2338

N Agarwal, J Brugarolas, P Ghatalia, S George, J B Haanen, H Gurney, R Ravilla, A Van der Veldt, B Beuselinck, I Pokataev, B B M Suelmann, M H Tuthill, D Vaena, F Zagouri, J Wu, R F Perini, Y Liu, J Merchan, M B Atkins

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Abstract

Background: Belzutifan is a first-in-class hypoxia-inducible factor subunit 2α (HIF-2α) inhibitor approved at a dose of 120 mg once daily for certain adults with VHL disease and adults with advanced renal cell carcinoma (RCC) following therapy with a programmed cell death protein 1 (PD-1) [or programmed death ligand 1 (PD-L1)] inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor. However, whether the belzutifan dose could be optimized is unclear.

Patients and methods: The phase II LITESPARK-013 study (NCT04489771) enrolled patients with advanced clear cell RCC whose disease progressed after one to three prior systemic therapies, including an anti-PD-(L)1 regimen. Patients were randomly assigned 1 : 1 to receive belzutifan 120 or 200 mg once daily. The primary endpoint was the objective response rate (ORR) per RECIST version 1.1. The secondary endpoints were duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

Results: Overall, 154 patients were enrolled (120 mg: n = 76; 200 mg: n = 78). The median follow-up was 20.1 months (range 14.8-28.4). The ORR was 23.7% versus 23.1% for the 120 mg and 200 mg groups, respectively [P = 0.5312; -0.5%, 95% confidence interval (CI) -14.0% to 12.9%]. The median DOR was not reached for the 120 mg arm and was 16.1 months (2.1+ to 23.5+) for the 200 mg arm. No between-group differences were observed for PFS [hazard ratio (HR) 0.94, 95% CI 0.63-1.40] or OS (medians not reached; HR 1.11, 95% CI 0.65-1.90). Grade 3 or 4 treatment-related adverse events were observed in 35 patients (46.1%) in the 120 mg group and 36 patients (46.2%) in the 200 mg group.

Conclusions: The efficacy of belzutifan was similar between the 120 mg dose and the 200 mg dose for previously treated clear cell RCC. Safety at both doses was consistent with the known safety profile of belzutifan. These results further support 120 mg once daily as the preferred dose for belzutifan.

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贝珠替凡治疗晚期透明细胞肾细胞癌患者的随机 2 期剂量比较 LITESPARK-013 研究。

背景：贝珠替凡是一种首创的HIF-2α抑制剂，获批剂量为120毫克，每日一次，适用于某些患有VHL疾病的成人，以及在接受程序性死亡受体（或配体）-1（PD-[L]1）抑制剂和血管内皮生长因子酪氨酸激酶抑制剂治疗后患有晚期肾细胞癌（RCC）的成人。然而，尚不清楚能否优化贝珠替凡的剂量：2期LITESPARK-013研究（NCT04489771）招募了晚期透明细胞RCC患者，这些患者在接受过1-3次系统治疗（包括抗PD-（L）1方案）后病情出现进展。患者按1:1的比例随机分配接受belzutifan 120毫克或200毫克治疗，每天一次。主要终点是RECIST v1.1标准规定的客观反应率（ORR）。次要终点包括反应持续时间（DOR）、无进展生存期（PFS）、总生存期（OS）和安全性：共有 154 名患者入选（120 毫克：76 人；200 毫克：78 人）。中位随访时间为 20.1 个月（14.8-28.4 个月）。120 毫克组和 200 毫克组的 ORR 分别为 23.7% 和 23.1%（P = 0.5312；-0.5% [95% CI，-14.0 至 12.9]）。120 毫克组未达到中位 DOR，200 毫克组为 16.1 个月（2.1+ 至 23.5+）。在 PFS（HR 0.94 [95% CI 0.63-1.40]）或 OS（未达到中位数；HR 1.11 [95% CI, 0.65-1.90]）方面未观察到组间差异。120毫克组35名患者（46.1%）和200毫克组36名患者（46.2%）出现了3级或4级治疗相关不良事件：结论：对于既往接受过治疗的透明细胞RCC，贝珠替凡120毫克剂量和200毫克剂量的疗效相似。两种剂量的安全性均符合贝珠替凡的已知安全性特征。这些结果进一步支持将120毫克每日一次作为贝珠替凡的首选剂量。

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

Annals of Oncology 医学-肿瘤学

CiteScore

63.90

自引率

1.00%

发文量

3712

审稿时长

2-3 weeks

期刊介绍： Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine. The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings. Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.