Testing Cabozantinib, Crizotinib, Savolitinib and Sunitinib in Kidney Cancer Which Has Progressed

Summary

This phase II trial studies how well cabozantinib s-malate, crizotinib, savolitinib, or sunitinib malate work in treating patients with kidney cancer that has spread from where it started to nearby tissue or lymph nodes or to other places in the body. Cabozantinib s-malate, crizotinib, savolitinib, and sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving cabozantinib s-malate, crizotinib, or savolitinib will work better in treating patients with kidney cancer compared to sunitinib malate.

Timeline

Start

2016-07-25

Primary completion

2023-10-19

Completion

2023-10-19

Outcome

Met primary endpoint

paper PFS was longer in patients in the cabozantinib group (median 9·0 months, 95% CI 6-12) than in the sunitinib group (5·6 months, 3-7; hazard ratio for progression or death 0·60, 0·37-0·97, one-sided p=0·019). PMID 33592176 ↗

registry analysis (superiority test); Sunitinib vs Cabozantinib; p = 0.019; Hazard Ratio (HR) 0.60 (95% CI 0.37 to 0.97); Regression, Cox NCT02761057 ↗

release “In the new findings, CABOMETYX demonstrated significant improvement in progression-free survival (PFS), the trial’s primary endpoint, and objective response rate (ORR) compared with sunitinib.” exelixis.com ↗

Publications

• Barata P, Tangen C, Plets M, Thompson IM Jr, Narayan V, George DJ, Heng DYC, Shuch B, Stein M, Gulati S, Tretiakova M, Tripathi A, Bjarnason GA, Humphrey P, Adeniran A, Vaishampayan U, Alva A, Zhang T, Cole S, Lara PN Jr, Lerner SP, Balzer-Haas N, Pal SK. Final Overall Survival Analysis of S1500: A Randomized, Phase II Study Comparing Sunitinib With Cabozantinib, Crizotinib, and Savolitinib in Advanced Papillary Renal Cell Carcinoma. J Clin Oncol. 2024 Nov 20;42(33):3911-3916. doi: 10.1200/JCO.24.00767. Epub 2024 Sep 10.
• Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.
• Pal SK, Tangen C, Thompson IM Jr, Balzer-Haas N, George DJ, Heng DYC, Shuch B, Stein M, Tretiakova M, Humphrey P, Adeniran A, Narayan V, Bjarnason GA, Vaishampayan U, Alva A, Zhang T, Cole S, Plets M, Wright J, Lara PN Jr. A comparison of sunitinib with cabozantinib, crizotinib, and savolitinib for treatment of advanced papillary renal cell carcinoma: a randomised, open-label, phase 2 trial. Lancet. 2021 Feb 20;397(10275):695-703. doi: 10.1016/S0140-6736(21)00152-5. Epub 2021 Feb 13.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Cabozantinib	Small molecule	60 mg	Oral
Subject	Crizotinib	Small molecule	250 mg	Oral
Subject	Savolitinib	Small molecule	600 mg	Oral
Subject	Sunitinib	Small molecule	50 mg	Oral

Indications