Outcomes of patients with metastatic clear-cell renal cell carcinoma treated with pazopanib after disease progression with other targeted therapies

Eur J Cancer. 2013 Oct;49(15):3169-75. doi: 10.1016/j.ejca.2013.06.003. Epub 2013 Jun 26.

Abstract

Aim: The multi-tyrosine kinase inhibitor pazopanib prolongs progression-free survival (PFS) versus placebo in treatment-naive and cytokine-refractory metastatic clear-cell renal cell carcinoma (ccRCC). Outcomes and safety data with pazopanib after targeted therapy (TT) are limited.

Methods: We retrospectively evaluated records of consecutive patients with metastatic ccRCC who had progressive disease (PD) after TT and received pazopanib from November 2009 through November 2011. Tumour response was assessed by a blinded radiologist using Response Evaluation Criteria In Solid Tumours (RECIST). PFS and overall survival (OS) were estimated by Kaplan-Meier methods.

Results: Ninety-three patients were identified. Median number of prior TTs was 2 (range, 1-5). There were 68 events (PD or death). Among 85 evaluable patients, 13 (15%) had a partial response. Median PFS was 6.5 months (95% CI: 4.5-9.7); median OS was 18.1 months (95% CI: 10.26-NA). Common adverse events (AEs) included fatigue (44%), elevated transaminases (35%), diarrhoea (30%), hypothyroidism (18%), nausea/vomiting (17%), anorexia (14%) and hypertension exacerbation (14%); 91% of AEs were grade 1/2. Eleven patients (12%) discontinued therapy due to AEs. There were no treatment-related deaths.

Concluding statement: Pazopanib demonstrated efficacy in patients with metastatic ccRCC after PD with other TTs. Toxicity overall was mild/moderate and manageable.

Keywords: Angiogenesis; Mammalian target of rapamycin; Metastatic renal cell carcinoma; Pazopanib; Targeted therapy; Tyrosine kinase inhibitor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Humans
  • Indazoles
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Retrospective Studies
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*

Substances

  • Angiogenesis Inhibitors
  • Indazoles
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Sulfonamides
  • pazopanib

Supplementary concepts

  • Clear-cell metastatic renal cell carcinoma