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Sequential therapy in metastatic clear cell renal carcinoma: TKI-TKI vs TKI-mTOR

Alessandra Felici1, Emilio Bria, Giampaolo Tortora

  • 1Division of Medical Oncology A, Regina Elena National Cancer Institute,Via Elio Chianesi 53, 00144, Rome, Italy.

Expert Review of Anticancer Therapy
|December 21, 2012
PubMed

Insights

For metastatic renal cell carcinoma, this review compares continuous VEGF/VEGFR inhibition versus alternating VEGFR and mTOR pathways. Evidence from clinical trials and preclinical studies informs optimal treatment strategies.

Area of Science:

  • Oncology
  • Medical Research
  • Pharmacology

Background:

  • Metastatic renal cell carcinoma (mRCC) treatment landscape includes seven approved targeted agents.
  • Agents target either the VEGF/VEGFR axis or the mTOR pathway.
  • Optimal sequencing or combination of these agents remains under investigation.

Purpose of the Study:

  • To review evidence comparing continuous VEGF/VEGFR inhibition (TKI-TKI) versus alternating VEGFR and mTOR inhibition (TKI-mTOR) in mRCC.
  • To address the optimal use of targeted agents in mRCC treatment.
  • To identify gaps in current evidence and explore supporting data.

Main Methods:

  • Review of randomized Phase III clinical trials.
  • Analysis of evidence from small-size, single-arm Phase II studies.
  • Inclusion of retrospective series and preclinical evidence.

Main Results:

  • Limited direct comparative evidence from Phase III trials exists.
  • Phase II and retrospective data provide insights into TKI-TKI and TKI-mTOR strategies.
  • Preclinical evidence may support the rationale for either approach.

Conclusions:

  • The optimal sequence or combination of VEGF/VEGFR and mTOR inhibitors in mRCC requires further elucidation.
  • Evidence synthesis suggests a complex decision-making process for clinicians.
  • Future research should focus on generating robust data to guide treatment selection.

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