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Cabozantinib for the treatment of renal cell carcinoma

Bernard Escudier1, Julie C Lougheed2, Laurence Albiges1

  • 1a Department of Medical Oncology , Gustave Roussy , Villejuif , France.

Expert Opinion on Pharmacotherapy
|November 12, 2016
PubMed
Abstract

Insights

Cabozantinib demonstrates improved progression-free survival, overall survival, and objective response rates in advanced renal cell carcinoma (RCC) patients previously treated with VEGFR-tyrosine kinase inhibitors. It shows promise as a leading second-line therapy and potentially in the first-line setting.

Area of Science:

  • Oncology
  • Pharmacology
  • Medical Science

Background:

  • Advanced renal cell carcinoma (RCC) treatments include VEGF/mTOR inhibitors and nivolumab.
  • Cabozantinib, a MET, VEGF, and AXL inhibitor, is FDA/EC-approved for advanced RCC post-VEGFR-TKI therapy.
  • This review covers cabozantinib's preclinical data, pharmacokinetics, and clinical outcomes in advanced RCC.

Purpose of the Study:

  • To review the preclinical development, scientific rationale, pharmacokinetics, and clinical efficacy/safety of cabozantinib for advanced RCC.
  • To discuss cabozantinib's role in clinical practice amidst evolving advanced RCC treatment options.
  • To provide expert opinion on cabozantinib's position in the treatment landscape.

Main Methods:

  • Review of preclinical data and scientific rationale.
  • Analysis of pharmacokinetic studies.
  • Evaluation of clinical trial data (Phase 2 and Phase 3) on efficacy and safety.

Main Results:

  • Cabozantinib improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus everolimus in a Phase 3 trial.
  • It is the only therapy to show improved PFS, ORR, and OS after prior antiangiogenic therapy in a pivotal Phase 3 trial.
  • Preliminary Phase 2 data suggest efficacy in untreated poor- and intermediate-risk RCC patients.

Conclusions:

  • Cabozantinib is a significant advancement for advanced RCC, particularly after prior VEGFR-TKI therapy.
  • Clinical data suggest cabozantinib may be the most effective tyrosine kinase inhibitor (TKI) for second-line treatment.
  • Further investigation into cabozantinib's first-line use is warranted based on encouraging preliminary results.
Keywords:
CabozantinibMETEORTKIVEGFRrenal cell carcinoma

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