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Top Line: What is the best first-line treatment option for advanced  clear cell renal cell carcinoma (RCC)?

The Study: Immunotherapy and TKI combinations have taken a leading role in the treatment of clear cell RCC. In Merck’s Keynote-426, axitinib + pembro showed a significant improvement in response rate and survival compared to sunitinib. BMS’s cabozantinib (TKI) and nivolumab (PD-1 inhibitor) are each second-line treatment options for clear cell RCC, and combination nivolumab and ipilimumab is a first-line option for patients with intermediate and poor risk clear cell RCC. The CheckMate-9ER trial compared first-line sunitinib (because easy target) with combination cabozantinib + nivolumab in over 650 patients with any risk clear cell RCC. The cabo+nivo combo doubled objective response rate 27→ 55%, doubled median PFS 8.3→ 16.6 months, and significantly improved 1-year OS 76→ 86%. These results are comparable to those seen in the Keynote-426 trial. Overall toxicity rates were similar between arms with the exception of increased liver toxicity in the combination arm. Quality of life was better with cabo+nivo, or rather it was maintained while QoL significantly declined in the sunitinib arm. So, there are now two effective immunotherapy/TKI combination options for first-line treatment of any risk clear cell RCC.

TBL: Combination cabozantinib and nivolumab significantly improved response rate, progression-free survival, and overall survival while maintaining quality of life compared to sunitinib for first-line treatment of clear cell RCC across risk groups. | Choueiri, N Engl J Medk 2021