EIKCS 2021: Combination therapies for metastatic kidney cancer: Which Approach?

The use of combination therapies for the first-line treatment of metastatic renal cell carcinoma (RCC) has increased significantly over the past 3 years. However, there are now a number of potential first-line treatments, and choosing the most suitable treatment for each individual patient can be difficult.

In a presentation at the European International Kidney Cancer (EIKC) 2021 Virtual Annual Meeting, Dr Brian Rini from Vanderbilt University Medical Center in the USA described on how to choose between a combination of targeted therapies, such as vascular endothelial growth factor (VEGF) inhibitors, plus immunotherapy or a combination of immunotherapies.

Dr Rini compared data from various studies of combination therapies, including IMmotion151, CheckMate214, KEYNOTE-426, CheckMate9ER, and CLEAR.

Each of these trials has shown a clear benefit for combination therapies compared to sunitinib, with a relative benefit of 30-35%. Survival at both 12 months and 24 months was similar for the combination therapies, although slightly improved with the combination of lenvatinib and pembrolizumab.

Combinations including a VEGF inhibitor resulted in more shrinkage of the cancer and a longer time to when the treatment stopped working and the cancer started growing again (progression-free survival) compared to the combination of nivolumab and ipilimumab. Complete response rates were around 10% with combination treatments, and slightly higher with lenvatinib and pembrolizumab.

About a third of patients on the nivolumab plus ipilimumab combination had long-term progression-free survival and duration of response after 3 and a half years follow-up. This shows that there is a group of patients who respond better to immunotherapy. Also, this highlights the durability of immunotherapy.

However, one of the drawbacks to these combination treatments is the side effects. Dr Rini suggested that a treatment-free interval could help with side effects and studies are ongoing to look at this effect in more detail.

Finally, Dr Rini described a study investigating biomarkers for the use of combination therapies to provide personalised therapy for metastatic RCC patients.

In conclusion, RCC responds to both VEGF inhibitors and immunotherapies. In the past few years, combination therapies based on immunotherapy have transformed the management of first-line metastatic RCC and all patients should be offered one of these approaches. Sunitinib is no longer considered the standard of care for metastatic RCC.

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