ASCO GU 2022: CABOSEQ: The Efficacy of Cabozantinib Post Up-Front Immuno-Oncology Combinations in Patients with Advanced Renal Cell Carcinoma: Results from the IMDC

( The 2022 GU ASCO Annual meeting included a renal cell carcinoma (RCC) session highlighting work from Dr. Vishal Navani and investigators presenting results of CABOSEQ assessing the efficacy of cabozantinib post up-front immuno-oncology combinations in patients with advanced RCC from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). There are limited data to understand the activity of cabozantinib as second line therapy post standard of care ipilimumab + nivolumab or immuno-oncology(IO)/vascular endothelial growth factor (VEGF) inhibitor combinations. The activity of subsequent third line approved therapies post cabozantinib has not been established.

Using the IMDC dataset, Dr. Navani and colleagues examined all patients who received second line cabozantinib. The objective was to identify the overall response rate (ORR), time to treatment failure (TTF), and overall survival (OS) of second line cabozantinib after ipilimumab + nivolumab, approved IO/VEGF combinations and other first line approaches. Additionally, they examined these outcomes for patients that received an approved third line treatment post second line cabozantinib. Hazard ratios were adjusted for IMDC risk groups.

There were 346 patients identified who had all received second line cabozantinib (78 post first line ipilimumab + nivolumab, 46 post first line IO/VEGF, and 222 post first line other). Of the entire cohort, 12.6%, 62.6% and 24.8% were IMDC favorable, intermediate and poor risk, respectively. There were 84% of patient that had clear cell histology, 18.5% had a sarcomatoid component, and 38.3% had bone metastases at diagnosis. Outcomes for patients that received second line cabozantinib, stratified by first line therapy, followed by outcomes for patients that received subsequent third line therapy post second line cabozantinib are outlined as follows:

Vishal Navani-0.jpg 

After adjustment for IMDC criteria, the HR for second line cabozantinib OS and TTF for IO/VEGF vs ipilimumab + nivolumab was 1.73 (95% CI 0.83-3.62 p = 0.14) and 1.62 (0.89-2.95 p = 0.11), respectively. There was no difference in OS for patients receiving second-line cabozantinib stratified by first line therapy: 

Vishal Navani-1.jpg 

As follows is the Sankey diagram outlining the treatment sequence for all patients receiving second-line cabozantinib:

Vishal Navani-2.jpg 

Dr. Navani concluded this presentation of CABOSEQ with the following summary statements:

  • There is clinically meaningful activity of cabozantinib post ipilimumab + nivolumab, IO/VEGF and other standard first line approved therapies
  • Broadly, time to event endpoints and response rates are similar irrespective of first line therapy
  • Approved systemic therapies post cabozantinib, mainly single agent VEGF inhibitors also have activity, though as expected this is diminished compared to earlier lines of therapy
  • These are real world benchmarks with which to counsel our patients when using single agent cabozantinib

Presented by: Vishal Navani, MBBS, MRCP, Tom Baker Cancer Center, University of Calgary, Calgary, AB, Canada

Co-Authors: Connor Wells, Devon J. Boyne, Winson Y. Cheung, Darren Brenner, Bradley Alexander McGregor, Chris Labaki, Andrew Lachlan Schmidt, Rana R. McKay, Sumanta K. Pal, Luis A Meza, Frede Donskov, Benoit Beuselinck, Matthew Scott Ernst, Maxwell Otiato, Lisa Ludwig, Thomas Powles, Bernadett Szabados, Toni Choueiri, Daniel Yick Chin Heng

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022 

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