Belzutifan用于晚期透明细胞肾细胞癌患者的随机II期剂量比较LITESPARK-013研究。
Randomized phase II dose comparison LITESPARK-013 study of belzutifan in patients with advanced clear cell renal cell carcinoma.
作者信息
Agarwal N, Brugarolas J, Ghatalia P, George S, Haanen J B, Gurney H, Ravilla R, Van der Veldt A, Beuselinck B, Pokataev I, Suelmann B B M, Tuthill M H, Vaena D, Zagouri F, Wu J, Perini R F, Liu Y, Merchan J, Atkins M B
机构信息
Director, Genitourinary Oncology Program, Huntsman Cancer Institute, University of Utah (NCI-CCC), Salt Lake City.
Director, Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas; Department of Internal Medicine, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas.
出版信息
Ann Oncol. 2024 Dec;35(12):1148-1156. doi: 10.1016/j.annonc.2024.08.2338. Epub 2024 Sep 2.
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.
背景
贝佐蒂凡（belzutifan）是首个获批的缺氧诱导因子亚基2α（HIF-2α）抑制剂，用于特定的成年VHL病患者以及接受过程序性细胞死亡蛋白1（PD-1）[或程序性死亡配体1（PD-L1）]抑制剂和血管内皮生长因子酪氨酸激酶抑制剂治疗后的晚期肾细胞癌（RCC）成年患者，剂量为每日一次120毫克。然而，贝佐蒂凡的剂量是否可以优化尚不清楚。
患者和方法
II期LITESPARK-013研究（NCT04489771）纳入了晚期透明细胞RCC患者，这些患者在接受一至三种先前的全身治疗（包括抗PD-（L）1方案）后疾病进展。患者按1:1随机分配，接受每日一次120或200毫克的贝佐蒂凡治疗。主要终点是根据实体瘤疗效评价标准（RECIST）1.1版的客观缓解率（ORR）。次要终点是缓解持续时间（DOR）、无进展生存期（PFS）、总生存期（OS）和安全性。
结果
总体而言，共纳入154例患者（120毫克组：n = 76；200毫克组：n = 78）。中位随访时间为20.1个月（范围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%置信区间（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 +）。PFS[风险比（HR）0.94，95% CI 0.63 - 1.40]或OS（均未达到中位值；HR 1.11，95% CI 0.65 - 1.90）在两组之间未观察到差异。120毫克组35例患者（46.1%）和200毫克组36例患者（46.2%）观察到3级或4级治疗相关不良事件。
结论
对于先前治疗的透明细胞RCC，120毫克剂量和200毫克剂量的贝佐蒂凡疗效相似。两种剂量的安全性与贝佐蒂凡已知的安全性特征一致。这些结果进一步支持每日一次120毫克作为贝佐蒂凡的首选剂量。
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