Dr. McKay on Recent Advancements in the Frontline Treatment of Metastatic RCC

Rana R. McKay, MD, medical oncologist, associate professor of medicine, Moores Cancer Center, UC San Diego Health, discusses four key trials that have advanced the frontline treatment of advanced metastatic renal cell carcinoma (mRCC) in the modern era.

The phase 3 CheckMate-214 trial (NCT02231749) evaluated nivolumab (Opdivo) in combination with iplimumab (Yervoy) vs the VEGF TKI sunitinib (Sutent), which was the standard of care. Following this study, a series of phase 3 trials further investigating the use of immunotherapy-based doublets vs VEGF TKI monotherapy were conducted.

The KEYNOTE-426 (NCT02853331) trial investigated the combination of pembrolizumab (Keytruda ) plus axitinib (Inlyta) vs sunitinib, CheckMate-9ER (NCT03141177) tested nivolumab plus cabozantinib (Cabometyx) vs sunitinib, and the 3-arm CLEAR (NCT02811861) trial evaluated pembrolizumab plus lenvatinib (Lenvima) vs lenvatinib plus everolimus (Afinitor) vs sunitinib.

All 4 studies demonstrated improved overall survival (OS) in patients receiving an immunotherapy doublet compared with sunitinib. However, immunotherapy/VEGF combinations show higher objective response rates, progression-free survival (PFS), and lower primary progressive disease rates when compared with dual immunotherapy, indicating they are more beneficial as a short-term intervention. Conversely, the combination of nivolumab plus ipilimumab demonstrated better long-term durability, with a 60-month PFS rate of 30%. 

Ultimately, clinicians need to evaluate the potential short-term and long-term benefits of these regimens when determining the correct treatment strategy for patients with metastatic RCC.