Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma

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. [1]

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. [2]

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. [3]

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. [4]

Title: Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma [5]
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
Characteristic Cabozantinib

(n = 187)


(n = 188)

Median age, years (range) 62 (36 – 83) 61 (31 – 84)
Male, n 142 130
Female, n 45 57
Geographic region
Europe, n 83 84
North America, n 76 64
Asia – Pacific, n 25 36
Latin America, n 3 4
White, n 157 147
Asian, n 12 20
Black, n 4 2
Other, n 10 6
Not reported, n 4 12
Prior VEGFR tyrosine kinase inhibitors
1, n 137 136
≥ 2, n 50 52
Previous systemic therapy
Sunitinib, n 114 113
Pazopanib, n 87 78
Axitinib, n 28 28
Sorafenib, n 11 19
Bevacizumab, n 1 7
Interleukin-2, n 11 13
Interferon alfa, n 6 13
Nivolumab, n 9 11
Radiotherapy, n 56 61
Nephrectomy, n 156 153
Results Cabozantinib Everolimus
Median progression-free survival 7.4 months

(95% confidence interval [CI], 5.6 – 9.1)

3.8 months

(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. [5]

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.


  1. Cleveland Clinic. Accessed November 9, 2015.
  2. American Cancer Society. Accessed November 9, 2015.
  3. European Society for Medical Oncology. Accessed November 9, 2015.
  4. Cabozantinib [package insert]. San Francisco, CA: Exelixis, Inc.; 2012
  5. 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.

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s