Belzutifan Efficacy and Tolerability in Patients with Sporadic Metastatic Clear Cell Renal Cell Carcinoma.

Belzutifan, a hypoxia-inducible factor 2 alpha inhibitor, was approved initially for patients with von Hippel-Lindau disease and more recently for sporadic, metastatic clear cell renal cell carcinoma (ccRCC) based on the results of LITESPARK-005. There is a paucity of data regarding real-world experience with belzutifan in patients with sporadic, metastatic ccRCC. This study aims to describe clinical outcomes with belzutifan in patients with sporadic, metastatic ccRCC.

A retrospective study of 22 patients who received belzutifan at MD Anderson Cancer Center prior to the Food and Drug Administration approval was conducted. Progression-free survival (PFS) and objective response rate (ORR) were assessed by a blinded radiologist using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. PFS and overall survival (OS) were measured from belzutifan initiation.

The median follow-up time was 14.9 mo. Most patients had International Metastatic RCC Database Consortium intermediate-risk disease, more than three metastatic sites, and a median of five prior lines of treatment at initiation of belzutifan; all patients received prior immune checkpoint therapy (ICT) and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). The median PFS was 8.51 mo (95% confidence interval [CI] 0-18.4) and ORR was 36.4%. The median OS was 14.72 mo (95% CI 7.34-22.10). Of 22 patients, four (18.2%) patients required dose reductions and three (13.6%) patients discontinued belzutifan because of adverse drug events (ADEs). The most common ADEs were anemia (77.3%; 17/22) and hypoxia (36.4%; 8/22). There were no treatment-related deaths.

In a heavily pretreated cohort of patients with sporadic, metastatic ccRCC, belzutifan had meaningful clinical activity and was well tolerated. These real-world results add to the results of LITESPARK-005 and support the use of belzutifan after progression on ICT and VEGFR-TKIs.

Belzutifan is a new medicine used to treat a type of clear cell kidney cancer that has spread to other parts of the body (metastasized). A study at MD Anderson Cancer Center followed 22 patients who were treated with belzutifan, and found that it worked to control the cancer for almost 9 mo and caused the cancer to shrink in 36% of patients. This study confirms that belzutifan can be effective and safe, even after other treatments have not worked.

European urology focus. 2024 Sep 21 [Epub ahead of print]

Emily Wang, Eric S Rupe, Sagar S Mukhida, Andrew C Johns, Matthew T Campbell, Amishi Y Shah, Amado J Zurita, Jianjun Gao, Sangeeta Goswami, Eric Jonasch, Pavlos Msaouel, Nizar M Tannir, Andrew W Hahn

Pharmacy Clinical Programs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Abdominal Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: ., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: .