Temporal Characteristics of Adverse Events of Tivozanib and Sorafenib in Previously Treated Kidney Cancer.

Tivozanib, vascular endothelial growth factor receptor inhibitor, met the primary endpoint of improved progression free survival compared to sorafenib in the phase 3 TIVO-3 study in patients with previously treated metastatic renal cell carcinoma. In this study we sought to understand the temporal characteristics of treatment related adverse events (TRAEs) and frequency and timing of the dose modifications. In this open label, randomized, phase 3 TIVO-3 study, previously treated patients with a diagnosis of metastatic renal cell carcinoma and with measurable disease were included. Patients were randomized to receive either tivozanib 1.5 mg orally once daily in 4-week cycles or sorafenib 400 mg orally twice daily continuously. Based on updated safety analysis data (cutoff date of August 15, 2019), time to onset of the most commonly reported TRAEs, duration of toxicity, rate of dose modifications was calculated for each treatment arm. Overall, 350 patients were randomly assigned to receive tivozanib or sorafenib;173 patients from the tivozanib arm and 170 patients from the sorafenib arm were included in this analysis. Patients received a median of 11.9 cycles (336 days) and 6.7 cycles (192 days) of tivozanib and sorafenib, respectively. Dose reductions, interruptions and treatment discontinuations were 25%, 50%, and 21%, and 39%, 50%, and 30% in the tivozanib and sorafenib arms, respectively, with a longer time to onset of TRAEs in the tivozanib arm. Tivozanib was associated with less TRAEs, fewer dose modifications, a longer time to onset and a shorter duration of TRAEs compared to sorafenib.

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Disclosure Zeynep B. Zengin, MD and Sumanta K. Pal, MD has no conflicts of interest that might be relevant to the contents of this manuscript. Vijay Kasturi, MD: Employed by AVEO Oncology. David F. McDermott, MD: Honorrari: BMS, Pfizer, Merck, Alkernes, EMD Serono, Eli Lilly and company, Iovance, Eisai, Werewolf Therapeutics, Calithera Biosciences. Research funding: BMS, Merck, Genentech, Pfizer, Exelexis, X4 Pharma, Alkermes. Bernard Escudier, MD: Advisory: Pfizer, BMS, Ipsen, Aveo, Eisai Thomas E. Hutson, DO, PharmD: Consultant/ Advisory Board and Speaker for: Aveo, Pfizer, Exelexis, BMS, EMD Serono, Eisai, Jansen, Gilead, and Astellas Camillo Porta, MD: Consulting and/or participation in Speakers’ Bureau: Angelini Pharma, AstraZeneca, Bristol Myers Squibb, Eisai, EUSA Pharma, General Electric, Ipsen, Janssen, Merck, Merck Sharp & Dohme, Novartis, Pfizer; Expert Testimony: EUSA Pharma and Pfizer; Protocol Steering Committee Member: Merck Sharp & Dohme, Bristol Myers Squibb, Eisai, EUSA Pharma; received travel support from Roche. Elena Verzoni, MD: Consulting and/or speakers’ Bureau: Bristol Myers Squibb, Eisai, Janssen, Merck, MSD, Ipsen Michael B. Atkins, MD: Consuting: Eisai, Aveo, Pfizer, Werewolf, Fathom, Pneuma, Leads, Pyxis Oncology, PACT, Elpis, X4Pharma, ValoHealth, ScholarRock, Surface, Takeda, Simcha, Bristol Myers Squibb, Merck, Novartis, Pfizer, Roche, Exelixis, Iovance, Idera, Agenus, Asher Bio, Neoleukin, AstraZeneca, Calithera, SeaGen, SAB Bio and Sanofi. Equity Interest: Werewolf, Pyxis Oncology. Brian Rini, MD: Research Funding to Institution: Pfizer, Hoffman-LaRoche, Incyte, AstraZeneca, Seattle Genetics, Arrowhead Pharmaceuticals, Immunomedics, BMS, Mirati Therapeutics, Merck, Surface Oncology, Dragonfly Therapeutics, Aravive, Exelixis, Jannsen; Consulting: BMS, Pfizer, GNE/Roche, Aveo, Synthorx, Compugen, Merck, Corvus, Surface Oncology, 3DMedicines, Aravive, Alkermes, Arrowhead, GSK, Shionogi, Eisai, Nikang Therapeutics; Stock: PTC therapeutics