Safety and Efficacy of Tivozanib in First-Line mRCC: A Multicenter Compassionate-Use Study (Meet-Uro 16)

Oncology. 2021;99(12):747-755. doi: 10.1159/000515951. Epub 2021 Sep 28.

Abstract

Introduction: Tivozanib is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR-1), VEGFR-2, and VEGFR-3, recently approved in Europe for the first-line treatment of metastatic renal cell carcinoma (mRCC).

Methods: Retrospective analysis of safety and activity of tivozanib administered at 1.34 mg daily (3 weeks on, 1 week off) within a compassionate-use program to patients with mRCC with no prior systemic treatment in Italy.

Results: From August 2018 to April 2019, 64 patients have started tivozanib in 9 oncology units. The median age was 67.5 years (range 40-85), 62.5% males. According to International Metastatic Renal Cell Carcinoma Database Consortium criteria, 27.1% of patients were good prognosis, 57.6% intermediate, and 15.3% poor. Primary tumor had been removed in 71.9% of patients. Histology was clear cell 89%, papillary 4.7%, and unclassified 6.3%. The response rate was 34.4%, stable disease 40.6%, and progression 15.6%. Grade 3-4 toxicities were 7.8% hypertension, 4.7% anemia, 3.1% mucositis, 3.1% asthenia, 1.6% diarrhea, 1.6% anorexia, 1.6% worsening of renal function, and 3.1% cardiac events. Dose reduction to 0.89 mg was applied to 17.2% of patients, and the discontinuation rate due to toxicity was 5.8%. Median progression-free survival was 12.4 months, with 68.7% of patients alive at 12 months. The developing of hypertension predicted increased progression-free survival at multivariate analysis (HR, 0.128; 95% CI, 0.03-0.59; p = 0.008).

Conclusions: Tivozanib showed good activity and favorable safety profile in a real-world cohort of unselected patients with mRCC. Predictive biomarkers of response to antiangiogenic therapy are urgently needed in order to identify RCC patients who could still receive a monotherapy with VEGFR inhibitors in the first line.

Keywords: Hypertension; Metastatic renal cell carcinoma; Progression; Retrospective; Survival; Tivozanib; Toxicity.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / epidemiology
  • Carcinoma, Renal Cell / pathology
  • Compassionate Use Trials / methods*
  • Female
  • Humans
  • Hypertension / chemically induced
  • Hypertension / epidemiology
  • Italy / epidemiology
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / epidemiology
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Metastasis / drug therapy
  • Phenylurea Compounds / administration & dosage
  • Phenylurea Compounds / adverse effects*
  • Progression-Free Survival
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects*
  • Quinolines / administration & dosage
  • Quinolines / adverse effects*
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
  • Retrospective Studies

Substances

  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Quinolines
  • tivozanib
  • Receptors, Vascular Endothelial Growth Factor