Pharmacotherapy for treating metastatic clear cell renal cell carcinoma

ABSTRACT

Introduction: Over the past decade metastatic renal cell carcinoma (RCC) treatment landscape has dramatically evolved from the era of cytokines-based immunotherapy (which benefited very few patients, at the expenses of high toxicities) to the present era of targeted agents and novel immunotherapeutics, greatly improving the prognosis of our patients.

Areas covered: Here we have reviewed the present status of the medical treatment of metastatic RCC. To do this, we interrogated the Medline database, as well as the proceedings of the main Oncological and Urological conferences for the relevant trials coducted so far.

Expert opinion: Despite all the advances made in these relatively few years, further improvements are needed, since none of the available agents proved able to cure even a sigle metastatic RCC patient. In particular, advances are awaited from the results of ongoing trial of combinations of different immune checkpoint inhibitors and of immune checkpoint inhibitors with anti-VEGF/VEGFRs agents. Furthermore, a better understanding of the molecular escape pathways used by the tumor to overcome VEGFR blockade or immune activation will hopefully bring soon to the clinic more active, tailored treatments, to be used in second line and beyond.

KEYWORDS:

• Clear cell renal cell carcinoma
• immune checkpoint inhibitors
• metastatic disease
• mTOR inhibitors
• pharmacotherapy
• tyrosine kinase inhibitors

Article highlights

• Our comprehension of the complex mechanisms underlying RCC growth, spread and resistance to the different agents used to treat it, have lead to the develoment of six molecularly targeted agents which have dramatically changed, for the better, the natural history of this once orphan disease.

• More recently, improvements in the comprehension of the bidirectional relationship between the tumor and the immune system, which lead to the development of highly active second-generation immunotherapeutics, have added a powerful weapon to our therapeutic armamentarium.

• Further improvements are expected by the combination of this different strategies, although toxicity seems the main issue to overcome.

• Biomarkers which could predict those will (and won’t) respond to each different agent are badly needed to optimize the treatment and save resources in a therapeutic environment where economical issues are becoming more and more important.

• The development of novel agents, or of combinations of different agents, together with the possible development of active adjuvant treatments – with recent results needing confirmation – will realistically turn this scenario upside down soon.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.