Tivozanib Safety, Efficacy in Heavily Pretreated Patients With Advanced Clear Cell RCC

A retrospective study of patients with advanced clear cell renal cell carcinoma (accRCC) offers new understandings of the role of tivozanib in the current RCC treatment landscape.

Andrew Johns, MD, and colleagues found that tivozanib offers a modest clinical benefit in some patients who receive prior therapy. They presented their findings at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium.

Tivozanib is a tyrosine kinase inhibitor that predominantly targets vascular endothelial growth factor receptors. It is approved as a third- or later-line therapy for advanced RCC based on the TIVO-3 trial, which showed improved progression-free survival (PFS) compared with sorafenib. However, TIVO-3 was conducted before some novel therapies entered the treatment landscape for accRCC, including immune checkpoint-based therapies (ICT), cabozantinib, and lenvatinib/everolimus.

Dr. Johns and colleagues at the University of Texas MD Anderson Cancer Center performed a retrospective study of patients with accRCC treated with tivozanib at their institution from June 2021 to July 2023. They assessed objective response rate (ORR), clinical benefit rate (percentage of all treated patients who achieved a complete or partial response or had stable disease for ≥6 months), time on treatment (TOT), PFS, overall survival (OS), and safety.

A total of 30 patients were included in the analysis, and the median follow-up was 10.8 months. At treatment initiation, 77% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 23% had an ECOG performance status of at least 2; 53% and 47% had intermediate-risk and poor-risk disease by International mRCC Database Consortium, respectively; 83% had at least 3 metastatic sites; and 80% had undergone prior nephrectomy.

The median number of prior therapies was 4. All patients received prior ICT (30% nivolumab/ipilimumab), 40% received prior axitinib, 87% received prior cabozantinib, and 60% received prior lenvatinib with or without everolimus.

Among the 26 patients with evaluable radiographic response, 2 had confirmed partial response (ORR, 7.7%) and 5 had stable disease for at least 6 months (clinical benefit rate, 23.3%). The median TOT was 3.2 months, median PFS was 3.7 months, and median OS has not been reached. Thirteen patients had died at the time of analysis, researchers acknowledged.

Additionally, Dr. Johns and colleagues found that 7 patients required dose reduction due to treatment-related adverse events (TRAEs); 15 patients had at least 1 any-grade TRAE and 4 patients had any-grade hypertension. Six grade 3 or higher TRAEs were reported, including congestive heart failure (3), hypertension, mucositis, and gastrointestinal perforation.

While 5 patients were continuing treatment with tivozanib at the time of analysis, 20 had discontinued due to progressive disease, 3 for TRAEs and 2 for infection or worsening of prior ICT-mediated neuropathy.

“In this cohort of heavily pretreated patients with accRCC, tivozanib yielded a modest clinical benefit in a minority of patients who received prior ICT, cabozantinib, and lenvatinib/everolimus,” study authors concluded, adding that TRAEs were consistent with previously published reports.