The need for new algorithms of treatment sequencing in clear-cell metastatic renal cell carcinoma

ABSTRACT

Introduction: In recent years, the systemic treatment of patients with metastatic renal-cell carcinoma (mRCC) has undergone profound innovations, offering the availability of new drugs, and raising the bar of the survival expectation in this, previously, almost-always, incurable disease. The likeliness of reaching durable response and long-term survival is still closely linked to good clinical management and smart treatment sequencing, rather than to a single systemic treatment choice.

Areas covered: We review all systemic therapeutic options currently available, describe the evidence behind the current options available for mRCC patient treatment, and provide our personal cues to support clinical decisions.

Expert opinion: The IMDC classification is still the only widely validated tool for the choice of primary therapy. Other elements should then be considered for selecting patients who can still receive TKI monotherapy (good-risk patients) or who deserve an ‘all-at-once’ approach with TKI plus ICI (poor-risk patients with the high metastatic burden and poor-prognosis organ involvement, likely not able to achieve a second chance), identifying these two ‘extreme’ situations and setting all the other treatment choices on the basis of several nuances. In the second- and further-line settings, ad-hoc prospective trials are awaited.

KEYWORDS:

• Renal-cell carcinoma
• mRCC
• clear-cell RCC
• metastatic renal cancer
• kidney cancer
• systemic treatment
• treatment algorithm
• treatment sequence
• immune checkpoint inhibitors
• tyrosine kinase inhibitors

Declaration of interest

M Bersanelli has received, outside the present work, research funding (institutional) by Seqirus, Roche S.p.A., Pfizer and Novartis, honoraria as a speaker at scientific events (personal fees) by Astra Zeneca, Bristol-Myers Squibb (BMS), Novartis and Pfizer; as a consultant for the advisory role (personal fees) by Novartis, BMS, and Pfizer. S Buti received honoraria as a speaker at scientific events and advisory role by BMS, Pfizer; MSD, Ipsen, Roche S.p.A., Eli–Lilly, AstraZeneca, and Novartis; he also received research funding from Novartis. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.