How clinical practice is changing the rules: the sunitinib 2/1 schedule in metastatic renal cell carcinoma

ABSTRACT

Introduction: Currently, sunitinib is a standard of care in first-line treatment for metastatic renal cell carcinoma (mRCC). However, with the standard 4/2 schedule (sunitinib 50 mg/day; 4 consecutive weeks on treatment; 2 weeks’ rest), 50% of patients require dose reductions to mitigate toxicity, highlighting the need to investigate alternative dosing schedules that improve tolerability without compromising efficacy.

Areas covered: We present a concise critical review of published studies comparing the efficacy and safety of the 4/2 and 2/1 schedule (2 weeks on treatment; 1 week rest) for sunitinib. While all studies evaluating the 2/1 schedule have a low level of evidence, the results indicate that the 2/1 schedule improves tolerability compared with the 4/2 schedule, including significant reductions in the incidence of specific adverse events. It was not possible to make any definitive conclusions regarding efficacy due to methodologic limitations of these studies.

Expert commentary: In the absence of strong evidence supporting the safety and efficacy of the 2/1 schedule, we recommend that patients should be initiated on sunitinib therapy with the standard 4/2 schedule and only be switched to the 2/1 schedule after the development of dose-limiting toxicities from weeks 3–4 (cycle 1) of the 4/2 schedule cycle.

KEYWORDS:

• Angiogenesis inhibitors
• renal cell carcinoma
• standard of care
• sunitinib
• dose schedule

Declaration of interest

B Escudier has received honoraria from Pfizer, Novartis, BMS, Roche, Ipsen and Exelixis.S Bracarda has received honoraria from, Pfizer, Novartis, Bayer, BMS, Astellas, Exelixis, Roche and Ipsen. S Negrier has received honoraria from Pfizer, Novartis, Bayer, BMS, and GSK (institution). J Casper declares honoraria from Pfizer, Novartis, Bayer and Medac. C Porta has received honoraria from Pfizer, Novartis, Exelixis, Roche-Genentech, BMS and Peloton. M Schmidinger has received honoraria from Pfizer, Novartis, BMS, Exelixis, Roche, Astellas, AVEO and Eisai. J Larkin has received honoraria from Pfizer, Novartis, MSD, BMS, AZ, GSK, Eisai and Roche/Genentech. M Gross-Goupil has received honoraria from, Pfizer, Novartis, Bayer and Bristol-Myers Squibb. 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.

Additional information

Funding

Funding for medical writing support was provided by Pfizer Inc.