Dr Singer on the Safety of Perioperative Nivolumab and Cabozantinib in RCC

Eric A. Singer, MD, professor, Urology and Bioethics, director, the Division of Urologic Oncology, The Ohio State University Wexner Medical Center, The Ohio State University Comprehensive Cancer Center (OSUCC)–James, discusses the safety of perioperative nivolumab (Opdivo) and cabozantinib (Cabometyx) in patients with metastatic clear cell renal cell carcinoma (RCC).

After the combination demonstrated efficacy and safety in the frontline treatment of patients with advanced RCC during the phase 3 CheckMate 9ER trial (NCT03141177), Singer and colleagues investigated the use of nivolumab plus cabozantinib prior to cytoreductive nephrectomy in patients with metastatic clear cell RCC in the phase 2 Cyto-KIK trial (NCT04322955). Patients received 40 mg of cabozantinib per day and 480 mg of nivolumab once every 4 weeks for 12 weeks prior to surgery.

The goal of Cyto-KIK is to examine the safety and efficacy of pretreating patients with the combination before continuing it following surgery, Singer says. The primary end point of the trial is complete response rate, which differs from many other studies conducted in this setting for patients with RCC, Singer expands.

The safety of the regimen and the optimal time to stop treatment with cabozantinib prior to surgery was previously unknown, Singer says. Investigators used a rolling 3+3 design to examine different stoppage points for cabozantinib, starting with 3 weeks prior to surgery, then 2 weeks prior to surgery. No issues were observed when cabozantinib was held 3 weeks or 2 weeks prior to surgery, Singer explains.

Furthermore, in findings presented at the 2023 American Urological Association Annual Meeting, the immuno-oncology–TKI combination with cabozantinib held 2 weeks prior to surgery was safe in a presurgical setting. No treatment-related adverse effects were reported during or after surgery, and no patients required delays in resuming treatment with the doublet after surgery, Singer concludes.