Real-world Practice Patterns and Safety of Concurrent Radiotherapy and Cabozantinib in Metastatic Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

There is a paucity of data on the safety of cabozantinib use in combination with radiotherapy.

To report the practice patterns, safety, and efficacy of cabozantinib with radiotherapy in metastatic renal cell carcinoma (mRCC).

An international multicenter retrospective study was conducted. Patients with mRCC treated with cabozantinib at any line of therapy and who received radiotherapy between 30 d prior to the start date of cabozantinib and 30 d following discontinuation of cabozantinib, from 2014 to 2020, were included. Concurrent use was defined as the use of cabozantinib on radiotherapy treatment days during any course of radiotherapy.

The primary outcomes of interest were the rate of grade ≥3 adverse events (AEs) occurring within 90 d of receipt of radiotherapy. Secondary outcomes included hospitalization rate and patterns of cabozantinib and radiotherapy use. Baseline characteristics and AEs were presented descriptively.

A total of 127 consecutive patients were included. Most patients had clear cell histology (88%), had International Metastatic Renal Cell Carcinoma Database Consortium intermediate-risk disease (57%), and had received at least one prior line of therapy (93%). Of 127 patients, 67 (53%) received concurrent cabozantinib with radiotherapy, while the remaining held cabozantinib on radiotherapy days. Overall, grade 3-4 AEs occurred in 6.3% (n = 8/127) of patients. No grade 5 events were observed. In patients treated with conventional palliative radiotherapy (n = 88), the rate of grade 3-4 AEs in those who had concurrent versus those who had nonconcurrent cabozantinib was 6.3% (n = 3/48) versus 5.0% (n = 2/40). No patient was hospitalized due to radiotherapy-related toxicity. In patients treated with stereotactic ablative body radiotherapy (SABR; n = 50), the rate of grade 3-4 AEs in those who had concurrent versus those who had nonconcurrent cabozantinib was 3.6% (n = 1/28) versus 9.1% (n = 2/22). One patient in the nonconcurrent group was hospitalized due to muscle weakness suspected to be related to associated vasogenic edema 19 d after SABR for multiple brain metastases.

In this real-world study of patients with mRCC treated with cabozantinib, 53% of patients received radiotherapy concurrently, with few grade 3-4 AEs reported within 90 d of receiving radiotherapy. The use of radiotherapy and cabozantinib requires a risk-benefit assessment of patient and disease characteristics to optimize therapy regimens.

Our study reports the real-world experience of using radiotherapy in patients receiving cabozantinib for metastatic kidney cancer. Over half of the patients continued taking cabozantinib while receiving radiotherapy, and few patients developed serious side effects. The combined use of radiotherapy and cabozantinib requires a careful risk-benefit assessment to achieve optimal treatment outcomes.

European urology oncology. 2022 Oct 31 [Epub ahead of print]

Chun Loo Gan, Jiaming Huang, Elizabeth Pan, Wanling Xie, Andrew L Schmidt, Chris Labaki, Luis Meza, Gabrielle Bouchard, Haoran Li, Francesca Jackson-Spence, Carla Sánchez-Ruiz, Thomas Powles, Shruti A Kumar, Nicole Weise, William A Hall, Brent S Rose, Benoit Beuselinck, Cristina Suarez, Sumanta K Pal, Toni K Choueiri, Daniel Y C Heng, Rana R McKay

Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada., Dana-Farber Cancer Institute/Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA., University of California San Diego, La Jolla, CA, USA., City of Hope Comprehensive Cancer Center, Duarte, CA, USA., Division of Medical Oncology, Department of Internal Medicine, University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA., Barts Cancer Institute, Queen Mary University of London, London, UK., Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain., Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA., University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium., University of California San Diego, La Jolla, CA, USA. Electronic address: .