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.

&ldquo;This real-world cohort confirm the favourable risk-benefit balance of tivozanib in the first line treatment of mRCC,&rdquo; 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 &ge;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&rsquo; 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

&ldquo;Immunotherapy has recently changed the landscape of first-line treatment of RCC,&rdquo; the authors explained. &ldquo;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.&rdquo;


  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.
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