Cabozantinib versus everolimus in advanced renal cell carcinoma

By T. Choueiri, B. Escudier, T. Powles, P. Mainwaring, B. Rini, F. Donskov, H. Hammers, Thomas E. Hutson, Jae-Lyun Lee, K. Peltola and 14 more. New England Journal of Medicine, 2015

1,101 citations recorded by the source corpus.

Background Cabozantinib is an oral small molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL; each has been implicated in metastatic renal cell carcinoma (RCC) pathobiology or development of resistance to antiangiogenic drugs. This randomized open-label phase 3 trial evaluated the efficacy of cabozantinib compared to everolimus in RCC patients who progressed after VEGFR-targeted therapy. Methods The trial randomized 658 patients to receive cabozantinib at a dose of 60 mg daily, or everolimus at a dose of 10 mg daily. The primary endpoint was progression-free survival. Secondary efficacy endpoints were overall survival and objective response rate. Results Median progression-free survival was 7.4 months with cabozantinib and 3.8 months with everolimus. The risk of progression or death was 42% lower with cabozantinib compared to everolimus (hazard ratio, 0.58; 95% confidence interval [CI] 0.45 to 0.75; P < 0.001). Objective response rates were 21% with cabozantinib and 5% with everolimus (P < 0.001). A planned interim analysis showed that overall survival was improved with cabozantinib (hazard ratio, 0.67; 95% CI, 0.51 to 0.89; P = 0.005) but did not cross the significance boundary. Adverse events (grade 3 or 4, regardless of causality) were reported in 74% of cabozantinib patients and 65% of everolimus patients. Discontinuation of study treatment for adverse events occurred in 9.1% of cabozantinib patients and 10% of everolimus patients. Conclusions Cabozantinib improved progression-free survival compared to everolimus in RCC patients who progressed after VEGFR-targeted therapy.

View Paper: https://www.semanticscholar.org/paper/69d4b6dac3c4f659661728f72cf577100d10646c

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Citations in the corpus

• Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial. (2017, result): “Cabozantinib, an oral small-molecule inhibitor of tyrosine kinases, including VEGFRs, MET, and AXL,(19) was recently approved for the treatment of patients with RCC who have received prior antiangiogenic therapy on the basis of a phase III trial (METEOR; Metastatic Renal Cell Carcinoma Phase III Stu”
• Treatment of renal cell carcinoma: Current status and future directions (2017, unknown): “Thus, a confirmatory, randomized, open-label, phase 3 study (METEOR) of cabozantinib versus everolimus was conducted in 658 patients who had progressive ccRCC after treatment with a VEGFR TKI.(119) The median PFS was 7.”
• Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma (2018, unknown): “Fatigue 212 (45) 49 (10) 0 70 (30) 10 (4) 0 Nausea 147 (31) 10 (2) 0 42 (18) 4 (2) 0 Hypertension 137 (29) 73 (16) 1 (<1) 14 (6) 4 (2) 0 Vomiting 121 (26) 2 (<1) 0 28 (12) 6 (3) 0 Increase in aspartate aminotransferase level 105 (22) 51 (11) 4 (1) 27 (11) 15 (6) 1 (<1)”
• Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2010, background): “However, second-line treatment has been dramatically modified by the report of two large trials showing improvement in OS with nivolumab and cabozantinib [50-52] over everolimus.”
• Renal cell carcinoma (2017, background): “However, second-line treatment has been dramatically modified by the report of two large trials showing improvement in OS with nivolumab and cabozantinib [50-52] over everolimus.”
• Systemic therapy in metastatic renal cell carcinoma (2016, background): “Cabozantinib, a TKI that targets MET and VEGFR-2, is another new substance that has been tested in a phase 3 study (METEOR) as a second-line treatment for patients with mRCC that had received at least one TKI treatment [31].”
• Angiogenic signaling pathways and anti-angiogenic therapy for cancer (2023, background): “Up to now, cabozantinib has been ratified for several most common angiogenic carcinomas (NCT01908426, NCT01865747).(431,432) A randomized and open-label phase III clinical trial has shown that combination of immune checkpoint inhibitors with cabozantinib significantly improved the OS and PFS rates o”
• Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. (2019, background): “However, second-line treatment has been dramatically modified by the report of two large trials showing improvement in OS with nivolumab and cabozantinib [50-52] over everolimus.”