Cabozantinib for the treatment of patients with metastatic non-clear cell renal cell carcinoma: A retrospective analysis

Eur J Cancer. 2018 Nov:104:188-194. doi: 10.1016/j.ejca.2018.08.014. Epub 2018 Oct 28.

Abstract

Background: Cabozantinib prolongs overall survival (OS) and progression-free survival (PFS) in patients with metastatic clear cell renal cell carcinoma (RCC) that progressed on first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI). The role of cabozantinib has not been established in non-clear cell renal cell carcinoma (nccRCC).

Methods: This is a retrospective study of 30 patients with nccRCC who received cabozantinib from January 2013 to January 2017. Information collected included baseline characteristics, toxicity, dose reductions, PFS and OS. A fellowship trained abdominal radiologist, blinded to patient history and clinical data, assessed radiographic response using RECIST, v1.1.

Results: With a median follow-up of 20.6 months (95% confidence interval [CI]: 11.4-28.8), median PFS was 8.6 months (95% CI: 6.1-14.7), and median OS was 25.4 months (95% CI: 15.5-35.4). Of the 28 patients with measurable disease, 4 had partial responses (2 papillary, 1 chromophobe and 1 unclassified RCC), 18 had stable disease (64.2%) and 6 had progressive disease (21.4%), resulting in a 14.3% objective response rate and a 78.6% disease control rate. Two patients with papillary RCC who had experienced disease progression on savolitinib achieved durable partial response and stable disease, respectively, following treatment with cabozantinib. Of the 21 patients who started cabozantinib at 60 mg/d, 12 (57.1%) required dose reduction due to toxicity.

Conclusion: In this retrospective study, cabozantinib produced a clinically meaningful benefit in patients with metastatic nccRCC, the majority of whom had disease progression on prior VEGFR-TKIs. Prospective trials of cabozantinib in nccRCC are warranted.

Keywords: Cabozantinib; Non-clear cell; Renal cell carcinoma; Treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anilides / administration & dosage
  • Anilides / adverse effects
  • Anilides / therapeutic use*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / enzymology
  • Carcinoma, Renal Cell / secondary*
  • Diarrhea / chemically induced
  • Fatigue / chemically induced
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / enzymology
  • Male
  • Middle Aged
  • Molecular Targeted Therapy* / adverse effects
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Progression-Free Survival
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors
  • Proto-Oncogene Proteins c-met / genetics
  • Pyridines / administration & dosage
  • Pyridines / adverse effects
  • Pyridines / therapeutic use*
  • Retrospective Studies
  • Salvage Therapy

Substances

  • Anilides
  • Antineoplastic Agents
  • Neoplasm Proteins
  • Protein Kinase Inhibitors
  • Pyridines
  • cabozantinib
  • MET protein, human
  • Proto-Oncogene Proteins c-met