Compassionate Use Study Shows Activity, Manageable Safety Profile With Tivozanib in mRCC

Patients with metastatic renal cell carcinoma in a real-world cohort of a retrospective analysis demonstrated positive activity and a favorable safety profile when receiving frontline tivozanib.

Patients with metastatic renal cell carcinoma (mRCC) in a real-world cohort of a retrospective analysis demonstrated positive activity and a favorable safety profile when receiving frontline tivozanib (Fotivda).1

Of the 64 patients enrolled in the study, 22 (34.4%) achieved radiological partial response and 26 (40.6%) had stable disease. Ten (15.6%) patients progressed early and 6 were not evaluable. The median overall survival had not been reached and 44 (68%) patients were still alive at 12 months.

The estimated progression-free survival (PFS) was 10.9 months (95% CI, 9.3-12.4) at the median follow-up of 12.5 months. At that point, 32 patients had progressed or died. There was an association with improved PFS for patients who received surgery prior to treatment; PFS was at 12.2 and 7.3 months for those who did or did not undergo surgery, respectively (P=.004). Nearly 72% of patients who had surgery on their primary tumor prior to the study. Development of hypertension, the most frequent grade 3/4 adverse event (AE), in patients during treatment with tivozanib was also associated with better PFS, with a 6-month difference (14.4 months for patients with hypertension vs 8.4 without;P<.0005).

For this therapy, the most common grade 1/2 adverse events were asthenia/fatigue (65.6%), hypothyroidism (45.3%), and hypertension (34.4%). Hypertension was higher than the other grade 3/4 toxicity, at 7.8%, and the overall incidence of grade 3/4 AEs was 21.5%. Eleven (17.2%) patients required dose reductions due to AEs and the same number of patients had temporary interruptions of tivozanib.

“This real-world cohort confirm the favourable risk-benefit balance of tivozanib in the first line treatment of mRCC,” the investigators wrote in their conclusion.

Tivozanib, a selective tyrosine kinase inhibitor [TKI] of vascular endothelial growth factor 1 (VEGFR-1), VEGFR-2, and VEGFR-3, was administered to unselected patients daily at 1.34 mg for 3 weeks on and 1 week off. Any patients who required dose reduction received 0.89 mg daily.

Sixteen (25%) of patients had good prognosis, 34 (53.1%) had intermediate prognosis, and 9 (14.1%) had poor prognosis; 5 patients did not have score available. Scores were in line with the International mRCC Database Consortium. Eighty-nine percent of patients had clear cell mRCC, and the rest had papillary (4.7%) or unclassified (6.3%) mRCC.

The median age in the study was 67.5 years of age (range, 30-85), and 40 (62.5%) were men. Investigators also stratified patients by BMI by either ≥25 kg/m2and <25kg/m2, which was 31 (48.4%) and 28 (43.8%), respectively. There was a median of 63 ml/min for the patients’ creatine clearance.

The study was carried out in 9 oncology centers in Italy from August of 2018 to April of 2019 for compassionate use of tivozanib. In a previous study, tivozanib showed better PFS than sorafenib [Nexavar] in a randomized phase III clinical trial; median PFS was 11.9 months with tivozanib and 9.1 months with sorafenib [HR, 0.79; 95% CI, 0.63-0.99].2

A recent meta-analysis of 4 approved first-line TKIs, including tivozanib, showed a similar efficacy throughout, but tivozanib demonstrated a more favorable safety profile for grade 3/4 AEs.3

“Immunotherapy has recently changed the landscape of first-line treatment of RCC,” the authors explained. “Predictive biomarkers of response to antiangiogenic therapy are urgently needed in order to identify RCC patients who should receive VEGFR inhibitors in the first line.”


  1. Basso U, Procopio G, Fornarini G, et al. Safety and efficacy of tivozanib in first-line metastatic renal cell carcinoma: a multicenter compassionate use study.J Clin Oncol.2020;38(suppl 6):632. doi: 10.1200/JCO.2020.38.6_suppl.632.
  2. Motzer RJ, Nosov D, Eisen T, et al. Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial.J Clin Oncol. 2013;31(30):3791—3799. doi: 10.1200/JCO.2012.47.4940.
  3. Manz KM, Fenchel K, Eilers A, Morgan J, Wittling K, Dempke WCM. Efficacy and safety of approved first-line tyrosine kinase inhibitor treatments in metastatic renal cell carcinoma: a network meta-analysis.Adv Ther. 2020;37(2):730—744. doi: 10.1007/s12325-019-01167-2.