Olivia Horga, Mercer University College of Pharmacy
It is reported that renal cell carcinoma (RCC) accounts for 2% to 3% of all malignant diseases in adults. It is also reported that despite the earlier detection, the rate of RCC-related mortality has increased, suggesting that recurrence and advanced disease are responsible for mortality. 
The American Cancer Society reports that targeted therapies for kidney cancer, including everolimus, are used to treat advanced kidney cancers after other drugs have been tried. 
According to the European Society for Medical Oncology guidelines, everolimus is used after first-line treatment with vascular endothelial growth factor receptor (VEGF) targeted therapy. 
The proposed mechanism of action for cabozantinib classifies it as a potent inhibitor of proinvasive receptor tyrosine kinases. It is suggested that cabozantinib induces apoptosis of cancer cells and suppresses tumor growth metastasis, and angiogenesis. 
|Title: Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma |
|Design||Randomized, open-label, phase three trial; N = 658|
|Objective||To evaluate the efficacy of cabozantinib as compared with everolimus in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy|
|Study Groups||Patients with advanced or metastatic renal-cell carcinoma with a clear-cell component and measurable disease; cabozantinib group (n = 330); everolimus groups (n = 328); progression-free – survival population for the primary end-point analysis (n = 375)|
|Methods||Patients received either cabozantinib 60 mg daily or everolimus 10 mg daily; treatment continued as long as clinical benefit was observed or until development of toxic effects|
|Duration||Randomization to one of the treatment groups: August 2013 – November 2014; minimum follow-up for progression-free – survival population = 11 months; median duration of treatment: 7.6 months cabozantinib; 4.4 months everolimus|
|Primary Outcome Measure||Duration of progression free survival|
|Baseline Characteristics||Progression-free Survival Population|
(n = 187)
(n = 188)
|Median age, years (range)||62 (36 – 83)||61 (31 – 84)|
|North America, n||76||64|
|Asia – Pacific, n||25||36|
|Latin America, n||3||4|
|Not reported, n||4||12|
|Prior VEGFR tyrosine kinase inhibitors|
|≥ 2, n||50||52|
|Previous systemic therapy|
|Interferon alfa, n||6||13|
|Median progression-free survival||7.4 months
(95% confidence interval [CI], 5.6 – 9.1)
(95% CI, 3.7 – 5.4)
|Adverse Events||Common Adverse Events (grade three or four): cabozantinib, n = 226 (68%); everolimus, n = 187 ( 58%)|
|Serious Adverse Events (grade five): cabozantinib, n = 22 (7%); everolimus, n = 25 (8%); treatment-related: cabozantinib, n = 1 (0.5%) [death]; everolimus, n = 2 (1.1%) [aspergillus infection and aspiration pneumonia]|
|Percentage that Discontinued due to Adverse Events: 9% of patients who received cabozantinib; 10% of patients who received everolimus|
|Study Author Conclusions||Progression-free survival was longer with cabozantinib than with everolimus among patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy.|
The study suggests that patients who underwent treatment with cabozantinib had a longer progression-free survival than those treated with everolimus. The study also suggests that the death rate was 33% lower with cabozantinib than with everolimus. 
Considering that cabozantinib had greater efficacy in patients with RCC, patients who suffer from this malignancy may benefit from a course of therapy that includes cabozantinib.
- Cleveland Clinic. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/nephrology/renal-cell-carcinoma/. Accessed November 9, 2015.
- American Cancer Society. http://www.cancer.org/cancer/kidneycancer/detailedguide/kidney-cancer-adult-treating-targeted-therapy. Accessed November 9, 2015.
- European Society for Medical Oncology. http://www.esmo.org/Guidelines/Genitourinary-Cancers/Renal-Cell-Carcinoma. Accessed November 9, 2015.
- Cabozantinib [package insert]. San Francisco, CA: Exelixis, Inc.; 2012
- Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015;373(19):1814-23.