Robert A. Figlin, MD, FACP
As the future of renal cell carcinoma (RCC) treatment heads toward the combination of immune-oncology agents—such as nivolumab (Opdivo) and ipilimumab (Yervoy)—or the combination of targeted therapies with checkpoint inhibitors, balancing toxicity with predicted efficacious outcomes management remains a top concern for physicians, explains Robert A. Figlin, MD.
State of the Science Summit™ on Genitourinary Cancers, Figlin, director, Division of Hematology/Oncology, professor of biomedical sciences and medicine, Cedars-Sinai Medical Center, discussed the expanding RCC armamentarium and balancing the benefits and risks of standard and emerging treatments to achieve optimal outcomes.
OncLive: What new agents have entered the treatment landscape in kidney cancer?
Over the past decade and a half we have had tremendous progress in kidney cancer. Originally, there was the approval of high-dose interleukin-2 in 1992. Now, we have a whole series of agents targeting the VEGF-receptor pathway, such as sunitinib (Sutent), pazopanib (Votrient), cabozantinib (Cabometyx), and others. There are also commercially available agents targeting the mTOR pathway that are either replacing our [frontline] standard of care, such as cabozantinib, or are soon to replace our standard of care, such as the combination of ipilimumab and nivolumab. This…immuno-oncology approach to kidney cancer has resulted in improvements in progression-free survival (PFS), overall survival (OS), and the possibility of durable remissions.
What does the safety profile look like with some of these agents?
The agents we use in kidney cancer have pretty standard toxicity profiles, especially when they're inhibiting the VEGF pathway. They produce hypertension, hand-foot syndrome, fatigue, and some changes in endocrine function, such as hyperthyroidism. Over the past decade, doctors have come to understand how to manage the side effects and how to modify the treatments to maintain the effectiveness of the drugs.
How is intermittent dosing of sunitinib better versus continuous dosing of other agents in RCC?
Sunitinib was approved by the FDA in 2006 for continuous dosing for 4 weeks on and 2 weeks off (4/2). Since then, we have realized through retrospective analyses, prospective studies, and personal experience that the 2-weeks-on/1-week-off (2/1) schedule is equally effective. It produces less toxicity and has indications of improved efficacy, because we are able to maintain patients on full doses for a longer period of time. In my practice, I start people on the 4/2 schedule. If they require changes as a result of toxicity, I quickly switch to the 2/1 schedule rather than dose reductions.
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