CABOSEQ: The Effectiveness of Cabozantinib in Patients With Treatment Refractory Advanced Renal Cell Carcinoma: Results From the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

There are limited data evaluating the activity of cabozantinib (CABO) as second line (2L) therapy post standard of care ipilimumab-nivolumab (IPI-NIVO) or immuno-oncology(IO)/vascular endothelial growth factor inhibitor (VEGFi) combinations (IOVE).

Using the IMDC database, we sought to identify the objective response rate, time to treatment failure (TTF) and overall survival (OS) of 2L CABO after IPI-NIVO, IOVE combinations, pazopanib or sunitinib (PAZ/SUN) or other first line (1L) therapies. Multivariable Cox regression, adjusted for underlying differences in IMDC groups, was used to compare differences in OS for 2L CABO based on preceding therapy.

Three hundred and forty-six patients received 2L CABO (78 post IPI NIVO, 46 post IOVE, 161 post PAZ/SUN, 61 post Other). Of the entire cohort, 12.6%, 62.6%, and 24.8% were IMDC favourable, intermediate, and poor risk, respectively. Patients that received 1L IPI-NIVO had a median OS of 21.4 (95% CI, 12.1 - NE [Not evaluable]) months compared to 15.7 (95% CI, 9.3 - NE) months in 1L IOVE and 20.7 (95% CI, 15.6 - 35.6) months in 1L PAZ/SUN, P = .28. Median TTF from the initiation of 2L CABO in the overall population was 7.6 (95% CI, 6.6 - 9.0) months. We were unable to detect a significant difference in 2L CABO OS based on type of 1L therapy received: 1L IPI-NIVO (reference group) vs. 1L IOVE HR 1.73 (95% CI, 0.83 - 3.62 P = .14), 1L PAZ/SUN 1.16 (95% CI, 0.67 - 2.00 P = .60), however given the retrospective observational nature of this work a lack of sufficient power may contribute to this.

In a large real world dataset, we identified clinically meaningful activity of 2L CABO after all evaluated contemporary 1L therapies, irrespective of whether the 1L regimen included a VEGFi. These are real world benchmarks with which to counsel our patients.

Clinical genitourinary cancer. 2022 Jul 21 [Epub ahead of print]

Vishal Navani, J Connor Wells, Devon J Boyne, Winson Y Cheung, Darren M Brenner, Bradley A McGregor, Chris Labaki, Andrew L Schmidt, Rana R McKay, Luis Meza, Sumanta K Pal, Frede Donskov, Benoit Beuselinck, Maxwell Otiato, Lisa Ludwig, Thomas Powles, Bernadett E Szabados, Toni K Choueiri, Daniel Y C Heng

Tom Baker Cancer Centre, Calgary, Canada. Electronic address: ., BC Cancer Agency, Vancouver, Canada., University of Calgary, Calgary, Canada., Tom Baker Cancer Centre, Calgary, Canada; University of Calgary, Calgary, Canada., Dana Farber Cancer Institute, Boston, USA., University of California San Diego, Moores Cancer Center, La Jolla, United States., City of Hope Comprehensive Cancer Center, Duarte, United States., University Hospital of Southern Denmark, Esbjerg, Denmark., University Hospitals Leuven, Leuven, Belgium., University of Michigan, Ann Arbor, USA., Ipsen Biopharmaceuticals, Canada., Barts Cancer Institute, Queen Mary University of London, London, United Kingdom., Tom Baker Cancer Centre, Calgary, Canada.

Go Beyond the Abstract and Read a Commentary by the Authors