795PD - Detailed comparison of the safety of tivozanib versus sorafenib in patients with advanced/metastatic renal cell carcinoma (mRCC) from a phase 3 trial

Date 01 October 2012
Event ESMO Congress 2012
Session Genitourinary tumors, non-prostate (renal cancer)
Topics Anti-Cancer Agents & Biologic Therapy
Renal Cell Cancer
Presenter Tim Eisen
Authors T.Q.G. Eisen1, C.N. Sternberg2, P. Tomczak3, M. Harza4, V. Jinga5, B. Esteves6, R.J. Motzer7
  • 1Oncology Box 193 (r4), University of CambridgeAddenbrooke's Hospital, GB-CB2 0QQ - Cambridge/UK
  • 2Medical Oncology, San Camillo Forlanini HospitalDepartment of Medical Oncology, 152 - Roma/IT
  • 3Uniwersytet Medyczny, Klinika Onkologii, Poznań/PL
  • 4Oncology, Fundeni Clinical Institute, Bucharest/RO
  • 5Oncology, Universit of Medicine and Pharmacy 'Carol Davila', Bucharest/RO
  • 6Clinical Research, AVEO Pharmaceuticals, Cambridge/US
  • 7Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York/US



Tivozanib (TIVO), an oral tyrosine kinase inhibitor, potently and selectively inhibits vascular endothelial growth factor receptors 1, 2, and 3. A Phase 3 trial (TIVO-1) comparing TIVO with sorafenib (SOR) in patients (pts) with mRCC showed superior efficacy to SOR and a favorable safety profile with a low incidence of off-target adverse events (AEs). Here we provide detailed drug-related AE data from the TIVO-1 trial.


Pts were randomized 1:1 to TIVO 1.5 mg once daily for 3 weeks (wks) followed by 1 wk rest, or SOR 400 mg twice daily continuously in a 4-wk cycle. AEs were recorded from the time pts signed the informed consent until 30 days after last dose of study drug. Blood pressure (mm Hg) was measured after a 5-minute rest period and taken on Days 1 and 15 of Cycle 1, on Day 1 of subsequent cycles, at the end-of-treatment visit, and at the 30-day follow-up visit. Descriptive statistics of drug-related AEs are presented.


Pts on the TIVO arm (175 [67.6%]) had fewer drug-related AEs than pts on the SOR arm (214 [83.3%]). The most common (≥10%) drug-related AEs and discontinuations are shown in the table.

TIVO (n = 259) n (%) SOR (n = 257) n (%)
AE All Grades Grade ≥3 All Grades Grade ≥3
Hypertension 109 (42.1) 61 (23.6) 79 (30.7) 39 (15.2)
Dysphonia 47 (18.1) 11 (4.3)
Diarrhea 47 (18.1) 5 (1.9) 71 (27.6) 15 (5.8)
Hand–foot syndrome 34 (13.1) 5 (1.9) 137 (53.3) 43 (16.7)
Fatigue 28 (10.8) 7 (2.7) 28 (10.9) 7 (2.7)
Alopecia 6 (2.3) 53 (20.6)
Discontinuations 11 (4.2) 14 (5.4)

Hypertension was the most frequent TIVO-related AE but was easily managed with standard antihypertensives. Fewer pts in the TIVO arm had ≥Grade 3 drug-related AEs than in the SOR arm (94 [36.3%] and 131 [51.0%], respectively). Pts in the TIVO arm required fewer overall dose reductions than did pts in the SOR arm (36 [13.9%] vs 114 [44.4%], respectively). Two deaths in the TIVO arm were due to myocardial infarction; cardiac failure was responsible for 2 deaths in each arm.


Pts on the TIVO arm experienced more hypertension and dysphonia, but less diarrhea, hand-foot syndrome, alopecia and discontinuations than pts on the SOR arm. Pts on the TIVO arm also had fewer overall dose reductions. These data demonstrate that TIVO is well-tolerated in pts with mRCC.


T.Q.G. Eisen: Consultancy fee/honorarium: AVEO before trial period, Bayer Support for travel to mtgs for the study or other purposes: AVEO Board Membership: AVEO, Bayer (ad boards) Grants/pending: Bayer Payment for lectures, service on speakers bureau: Bayer.

C.N. Sternberg: Consultancy: Astellas.

B. Esteves: AVEO Pharmaceuticals employee with stock options.

R.J. Motzer: Consultant: Pfizer Research Funding: AVEO, GSK, Novartis.

All other authors have declared no conflicts of interest.