IKCS 2022: Assessment of Clavien-Dindo Classification in Patients with Metastatic Clear Cell Renal Cell Carcinoma Who Received Perioperative Cabozantinib and Nivolumab on Cyto-KIK Clinical Trial

(UroToday.com) The ninth session of the 2022 International Kidney Cancer Symposium (IKCS): North America meeting featured oral abstract presentations. In this context, Dr. Runcie presented on safety of cytoreductive nephrectomy following perioperative cabozantinib and nivolumab. In the interferon era, there was evidence of survival benefit of nephrectomy in patients with metastatic RCC. However, updated data from CARMENA among patients receiving sunitinib did not support the role of surgery in this patient population.

In the phase 2 Cyto-KIK trial, patients with mccRCC received cabozantinib (40mg daily) and nivolumab (480mg q4 weeks) for 12 weeks prior to cytoreductive nephrectomy. Post-operatively, patients resumed treatment with cabozantinib and nivolumab until disease progression. A 3+3 design was used to evaluate the safety of the interval (21 or 14 days) between the discontinuation of cabozantinib and nephrectomy. Each of the evaluable patients completed at least 10 of 14 cabozantinib doses in the two-week period prior to stopping pre-operative cabozantinib and surgical resection of the primary tumor.


In the Cyto-KIK trial, surgical outcomes, as measured using the Clavien-Dindo classification system, were a secondary endpoint.

To date, 16 patients have been enrolled and 14 have undergone nephrectomy. Among these patients, 75% are male, 25% female, and ages ranged from 44-77 years old with median age at diagnosis 58.5 years old. BMIs ranged from 17.8 kg/m2 to 39.3 kg/m2 with median BMI of 28.7kg/m2. 63% of patients were classified by IMDC as intermediate-risk and 37 % as poor-risk disease.

Of the 14 patients who completed nephrectomy, dose reductions occurred in 14% and cabozantinib was held for some duration of time in 42% of patients during the course of treatment. Three evaluable patients completed nephrectomy within the 21-day interval and 5 within the 14-day interval after discontinuation of cabozantinib.

There were no surgical complications as assessed by Clavien-Dindo Classification in patients who completed nephrectomy, including a patient who held cabozantinib 23 days prior to surgery due to Grade 3 renal mass hemorrhage.

Thus, the authors concluded that the combination of cabozantinib and nivolumab can be safely administered up to 14 days prior to cytoreductive nephrectomy. While 16 subjects are currently enrolled, the target enrollment is 42 and is ongoing.

Presented by: Karie Runcie, MD; New York Presbyterian Hospital, Columbia University

Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2022 International Kidney Cancer Symposium (IKCS) North America, November 4-5, Austin, Texas, USA 

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