On March 10, 2021, the FDA granted regular approval to tivozanib for treatment of patients with relapsed or refractory (R/R) advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. Approval was based on the TIVO-3 study, a randomized trial of tivozanib versus sorafenib in patients with R/R advanced RCC. In TIVO-3, patients were randomized to receive either tivozanib 1.34 mg orally once daily for 21 consecutive days of every 28-day cycle or sorafenib 400 mg orally twice daily continuously. The primary endpoint was progression-free survival (PFS) per RECIST v1.1. Tivozanib demonstrated efficacy compared with sorafenib with an improvement in PFS [HR: 0.73; 95% confidence interval (CI): 0.56-0.95; p=0.016]. The estimated median PFS was 5.6 months and 3.9 months in the tivozanib and sorafenib arms, respectively. There was no evidence of a detrimental effect on overall survival: HR 0.97 (95% CI: 0.75-1.24). The most common grade 3-4 adverse reaction on the tivozanib arm was hypertension (24%). Compared to sorafenib, tivozanib was associated with lower rates of grade 3-4 diarrhea, rash, and palmar-plantar erythrodysesthesia. Patients receiving tivozanib in TIVO-3 had lower rates of dose reduction, interruption, or permanent discontinuation than those receiving sorafenib.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2021 Aug 20 [Epub ahead of print]
Elaine Chang, Chana Weinstock, Lijun Zhang, Mallorie H Fiero, Miao Zhao, Eias Zahalka, Tiffany K Ricks, Jeanne Fourie Zirkelbach, Junshan Qiu, Jingyu Yu, Xiao Hong Chen, Vishal Bhatnagar, Kirsten B Goldberg, Shenghui Tang, Paul G Kluetz, Richard Pazdur, Amna Ibrahim, Julia A Beaver, Laleh Amiri-Kordestani
Center for Drug Evaluation and Research, United States Food and Drug Administration ., Center for Drug Evaluation and Research, United States Food and Drug Administration., Center for Drug Evaluation and Research, Food and Drug Administration., United States Food and Drug Administration., OFfice of Hematology and Oncology Products, United States Food and Drug Administration., Div. of Hematology Oncology Toxicology, United States Food and Drug Administration., CDER/OTS/OCP/DCPII, United States Food and Drug Administration., Office of Biostatistics, United States Food and Drug Administration., Office of Translational Sciences, United States Food and Drug Administration., Office of New Drugs Quality Assurance, United States Food and Drug Administration., Oncology Center of Excellence, United States Food and Drug Administration., CDER, United States Food and Drug Administration., Oncology Center of Excellence, Food and Drug Administration., Office of Oncology Drug Products, United States Food and Drug Administration., Office of Hematology and Oncology Products, Food and Drug Administration., Office of Hematology and Oncology, United States Food and Drug Administration., Division of Oncology Products 1, Food and Drug Administration Center for Drug Evaluation and Research.