Despite the advances in first-line treatments for metastatic renal cell carcinoma (RCC) over the past few years, new treatments are on the horizon. In a presentation at the European International Kidney Cancer (EIKC) 2021 Virtual Annual Meeting, Dr Hans Hammers from University of Texas Southwestern Medical Center in the USA discussed future treatments for metastatic RCC.

In the past few years, combination treatments including immunotherapy have become the standard of care. Recently lenvatinib plus pembrolizumab was found to be a very active treatment with an unusually long time of nearly 2 years to progression of the cancer.

Dr Hammers went on to summarise the safety and efficacy of a number of combination treatments, including nivolumab and ipilimumab, axitinib and pembrolizumab, and cabozantinib plus nivolumab. Dr Hammers noted that very few patients have progressive disease with either of the two most recently published combinations – cabozantinib and nivolumab or lenvatinib and pembrolizumab.

Since it is not clear how or when to choose between immunotherapy or immunotherapy/vascular endothelial growth factor (VEGF) inhibitor combinations an alternative is a triplet of cabozantinib, nivolumab and ipilimumab, which is being assessed in the COSMIC-313 study.

Dr Hammers went on to describe other treatments in development, such as bempegaldesleukin, a pegylated IL-2 molecule, in combination with nivolumab, a glutaminase inhibitor CB-839 in combination with cabozantinib, and the HIF-2 inhibitor belzutifan, which has shown some benefit in two-thirds of patients, as well as a durable response. Belzutifan is also being tested in VHL-associated RCC.

In addition, there is promise for the benefit of immunotherapy (pembrolizumab) as adjuvant treatment after nephrectomy.

In summary, Dr Hammers highlighted that the treatment options for metastatic RCC are rapidly expanding, with great promise for novel HIF-2 inhibitors and adjuvant immunotherapy.

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