Cabozantinib is approved for metastatic renal cell carcinoma (mRCC) based on the METEOR and CABOSUN trials. However, real-world effectiveness and dosing patterns of cabozantinib are not well characterized.
Patients with mRCC treated with cabozantinib between 2011 and 2019 were identified and stratified using the International mRCC Database Consortium (IMDC) risk groups. First- (1L), second- (2L), third- (3L), and fourth-line (4L) overall response rate (ORR), time to treatment failure (TTF), and overall survival (OS) were analyzed. Dose reduction rates and their association with TTF and OS were determined.
A total of 413 patients were identified. The ORRs across 1L to 4L were 32%, 26%, 25%, and 29%, respectively, and the median TTF rates were 8.3, 7.3, 7.0, and 8.0 months, respectively. The median OS (mOS) rates in 1L to 4L were 30.7, 17.8, 12.6, and 14.9 months, respectively. For patients treated with 1L PD(L)1 combination agent (n = 31), 2L cabozantinib had ORR of 22%, median TTF of 5.4 months, and mOS of 17.4 months. About 50% (129/258) of patients required dose reductions. The TTF and mOS were significantly longer for patients who required dose reduction vs. patients who did not, with an adjusted hazard ratio of 0.37 (95% CI 0.202-0.672, p < 0.01) and 0.46 (95% CI 0.215-0.980, p = 0.04), respectively. Limitations include the retrospective study design and the lack of central radiology review.
The ORR and TTF of cabozantinib were maintained from the 1L to 4L settings. Dose reductions due to toxicity were associated with improved TTF and OS. Cabozantinib has clinical activity after 1L Immuno-oncology combination agents.
Cancer medicine. 2021 Jan 18 [Epub ahead of print]
Chun Loo Gan, Shaan Dudani, J Connor Wells, Frede Donskov, Sumanta K Pal, Nazli Dizman, Nityam Rathi, Benoit Beuselinck, Flora Yan, Aly-Khan A Lalani, Aaron Hansen, Bernadett Szabados, Guillermo de Velasco, Ben Tran, Jae Lyun Lee, Ulka N Vaishampayan, Georg A Bjarnason, Mathushan Subasri, Toni K Choueiri, Daniel Y C Heng
Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada., Aarhus University Hospital, Aarhus, Denmark., City of Hope Comprehensive Cancer Center, Duarte, CA, USA., Huntsman Cancer Hospital, Salt Lake City, UT, USA., University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium., University of Texas Southwestern Medical Center, Dallas, TX, USA., Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada., Princess Margaret Cancer Centre, Toronto, ON, Canada., Queen Mary University of London, Barts Cancer Institute, London, UK., University Hospital 12 de Octubre, Madrid, Spain., Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Vic, Australia., Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea., Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA., Sunnybrook Odette Cancer Centre, Toronto, ON, Canada., London Ontario Health Sciences Centre, London, ON, Canada., Dana-Farber Cancer Institute/Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA.