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

Alessandra Felici, Emilio Bria, Giampaolo Tortora, Francesco Cognetti, Michele Milella

Research output: Contribution to journalArticlepeer-review


With seven targeted agents, directed against the VEGF/VEGF receptor (VEGFR) axis or the mTOR pathway, approved for the treatment of metastatic renal cell carcinoma and more active agents in advanced phase of clinical testing, questions have arisen with regard to their optimal use, either in combination or in sequence. One of the most compelling (and debated) issues is whether continued VEGF/VEGFR inhibition with agents hitting the same targets (TKI-TKI) affords better results than switching mechanisms of action by alternating VEGFR and mTOR inhibition (TKI-mTOR). In this article, the authors review the (little) available evidence coming from randomized Phase III clinical trials and try to fill in the (many) remaining gaps using evidence from small-size, single-arm Phase II studies and retrospective series, as well as reviewing preclinical evidence supporting either strategy.

Original languageEnglish
Pages (from-to)1545-1557
Number of pages13
JournalExpert Review of Anticancer Therapy
Issue number12
Publication statusPublished - Dec 2012


  • metastatic
  • mTOR inhibitors
  • renal cell carcinoma
  • second-line treatment
  • sequential therapy
  • VEGF receptor-tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Oncology


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