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Updated: Mar 29, 2026
Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
Published on: April 29, 2014
Targeted therapy for renal cell carcinoma: focus on 2nd and 3rd line
Camillo Porta1,2, Palma Giglione1, Chiara Paglino1,2
1a Medical Oncology , I.R.C.C.S. San Matteo University Hospital Foundation , Pavia , Italy.
Introduction:
Second- and third-line treatments are more and more frequently administered to metastatic renal cell carcinoma (mRCC) patients.
Areas Covered:
Here we discuss the various levels of evidence supporting presently available recommendations, trying to address a number of as yet unanswered issues, and also to take a glowing glance at the future. To do this, we interrogated the Medline database, as well as the proceedings of the main Oncological and Urological conferences for relevant studies.
Expert Opinion:
Until recently, with regard to choosing the second line treatment after the failure of therapy with vascular endothelial growth factor receptors-tyrosine kinase inhibitors (VEGFR-TKIs), the continued inhibition of the VEGF/VEGR pathway, or else the switch to an mTOR inhibitor, is recommended. These two options are characterized by partly different targets, completely different toxicity profiles, but a comparable efficacy. This scenario will change soon, after the publication of two randomized, controlled, phase III trials in which cabozantinib and nivolumab proved to be superior as compared to everolimus. As regards third line treatment, where a sequence of two VEGFR-TKIs has been used beforehand, the choice is represented by the mTOR inhibitor everolimus, whilst if a VEGFR-TKI followed by everolimus has been chosen, a return to VEGF pathway inhibition is suggested.
Insights
Second- and third-line treatments for metastatic renal cell carcinoma (mRCC) are evolving. New data show cabozantinib and nivolumab are superior to everolimus for second-line therapy, changing treatment recommendations.
Area of Science:
- Oncology
- Urology
- Pharmacology
Background:
- Metastatic renal cell carcinoma (mRCC) treatment increasingly involves second- and third-line therapies.
- Current treatment guidelines for mRCC are based on limited evidence and evolving research.
Purpose of the Study:
- To review current evidence for second- and third-line mRCC treatments.
- To address unanswered questions and explore future directions in mRCC therapy.
Main Methods:
- Systematic review of Medline database.
- Analysis of proceedings from major Oncological and Urological conferences.
Main Results:
- Second-line: Continued VEGF pathway inhibition or switching to an mTOR inhibitor were previously recommended.
- New phase III trials indicate cabozantinib and nivolumab are superior to everolimus for second-line treatment.
- Third-line: Everolimus is an option after two VEGFR-TKIs; VEGF pathway re-challenge is suggested after VEGFR-TKI plus everolimus.
Conclusions:
- Treatment paradigms for second- and third-line mRCC are shifting.
- Cabozantinib and nivolumab represent significant advancements in second-line therapy.
- Future mRCC treatment strategies will incorporate new evidence and targeted therapies.
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